SpringerLink
Log in

Pharmacology of Antihypertensive Drugs

  • Chapter
  • First Online:
Hypertension in the Dog and Cat

Abstract

The clinical pharmacology of antihypertensive drugs in general is reviewed. Particular attention is given to the drugs which inhibit renin-angiotensin-aldosterone system (RAAS) and the calcium channel blocker, amlodipine as these have been well characterised in cats and, to a certain extent, in dogs (RAAS inhibition) to support their therapeutic use in veterinary practice. Where available, data on the development of these drugs as veterinary products is presented.

This chapter highlights gaps in our knowledge about these groups of drugs and how they might be combined most effectively to manage hypertension clinically. Furthermore, central inhibitors of the sympathetic nervous system remain to be examined in veterinary patients as a way of managing hypertension associated with CKD in dogs and cats despite the likelihood that overactivity of the sympathetic nervous system play a significant part in the pathophysiology of hypertension in the renal patient (see Chap. 1).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

Notes

  1. 1.

    Dosing regimen in the US study was 1.5 mg/kg twice daily for 14 days followed by 2 mg/kg once daily.

References

  • Acierno MJ, Brown S, Coleman AE, Jepson RE, Papich M, Stepien RL, Syme HM (2018) ACVIM consensus statement: guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats. J Vet Intern Med 32(6):1803–1822

    PubMed  PubMed Central  Google Scholar 

  • Ahmad S, Varagic J, Groban L, Dell’Italia LJ, Nagata S, Kon ND, Ferrario CM (2014) Angiotensin-(1-12): a chymase-mediated cellular angiotensin II substrate. Curr Hypertens Rep 16(5):429

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ames MK, Atkins CE, Lantis AC, zum Brunnen J (2016) Evaluation of subacute change in RAAS activity (as indicated by urinary aldosterone:creatinine, after pharmacologic provocation) and the response to ACE inhibition. J Renin Angiotensin Aldosterone Syst 17(1):1470320316633897

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ames MK, Atkins CE, Eriksson A, Hess AM (2017) Aldosterone breakthrough in dogs with naturally occurring myxomatous mitral valve disease. J Vet Cardiol 19(3):218–227

    Article  CAS  PubMed  Google Scholar 

  • Batova S, DeWever J, Godfraind T, Balligand JL, Dessy C, Feron O (2006) The calcium channel blocker amlodipine promotes the unclam** of eNOS from caveolin in endothelial cells. Cardiovasc Res 71(3):478–485

    Article  CAS  PubMed  Google Scholar 

  • Berhane Y, Sent U, Elliott J (2009) Effect of telmisartan on angiotensin II-induced contraction of feline arteries. J Vet Pharmacol Ther 32:232 (abstract)

    Google Scholar 

  • Bernay F, Bland JM, Häggström J, Baduel L, Combes B, Lopez A, Kaltsatos V (2010) Efficacy of spironolactone on survival in dogs with naturally occurring mitral regurgitation caused by myxomatous mitral valve disease. J Vet Intern Med 24(2):331–341

    Article  CAS  PubMed  Google Scholar 

  • Bijsmans ES, Jepson RE, Chang YM, Syme HM, Elliott J (2015) Changes in systolic blood pressure over time in healthy cats and cats with chronic kidney disease. J Vet Intern Med 29(3):855–861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bijsmans ES, Doig M, Jepson RE, Syme HM, Elliott J, Pelligand L (2016) Factors influencing the relationship between the dose of amlodipine required for blood pressure control and change in blood pressure in hypertensive cats. J Vet Intern Med 30(5):1630–1636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bomback AS, Klemmer PJ (2007) The incidence and implications of aldosterone breakthrough. Nat Clin Pract Nephrol 3(9):486–492

    Article  CAS  PubMed  Google Scholar 

  • Bomback AS, Rekhtman Y, Klemmer PJ, Canetta PA, Radhakrishnan J, Appel GB (2012) Aldosterone breakthrough during aliskiren, valsartan, and combination (aliskiren + valsartan) therapy. J Am Soc Hypertens 6(5):338–345

    Article  CAS  PubMed  Google Scholar 

  • Bovee KC, Wong PC, Timmermans PB, Thoolen MJ (1991) Effects of the nonpeptide angiotensin II receptor antagonist DuP 753 on blood pressure and renal functions in spontaneously hypertensive PH dogs. Am J Hypertens 4(4 Pt 2):327S–333S

    Article  CAS  PubMed  Google Scholar 

  • Brown SA, Langford K, Tarver S (1997) Effects of certain vasoactive agents on the long-term pattern of blood pressure, heart rate, and motor activity in cats. Am J Vet Res 58(6):647–652

    CAS  PubMed  Google Scholar 

  • Brown SA, Brown CA, Jacobs G, Stiles J, Hendi RS, Wilson S (2001) Effects of the angiotensin converting enzyme inhibitor benazepril in cats with induced renal insufficiency. Am J Vet Res 62(3):375–383

    Article  CAS  PubMed  Google Scholar 

  • Brown SA, Finco DR, Brown CA, Crowell WA, Alva R, Ericsson GE, Cooper T (2003) Evaluation of the effects of inhibition of angiotensin converting enzyme with enalapril in dogs with induced chronic renal insufficiency. Am J Vet Res 64(3):321–327

    Article  CAS  PubMed  Google Scholar 

  • Buchwalder-Csajka C, Buclin T, Brunner HR et al (1999) Evaluation of the angiotensin challenge methodology for assessing the pharmacodynamics profile of antihypertensive drugs acting on the renin-angiotensin system. Br J Clin Pharmacol 48:594–604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chaugai S, Sherpa LY, Sepehry AA, Kerman SRJ, Arima H (2018) Effects of long- and intermediate-acting dihydropyridine calcium channel blockers in hypertension: a systematic review and meta-analysis of 18 prospective, randomized, actively controlled trials. J Cardiovasc Pharmacol Ther 23(5):433–445

    Article  CAS  PubMed  Google Scholar 

  • Christ DD, Wong PC, Wong YN, Hart SD, Quon CY, Lam GN (1994) The pharmacokinetics and pharmacodynamics of the angiotensin II receptor antagonist losartan potassium (DuP 753/MK 954) in the dog. J Pharmacol Exp Ther 268(3):1199–1205

    CAS  PubMed  Google Scholar 

  • Coleman AE, Brown SA, Stark M, Bryson L, Zimmerman A, Zimmering T, Traas AM (2018) Evaluation of orally administered telmisartan for the reduction of indirect systolic arterial blood pressure in awake, clinically normal cats. J Feline Med Surg

    Google Scholar 

  • Coleman AE, Brown SA, Traas AM, Bryson L, Zimmering T, Zimmerman A (2019) Safety and efficacy of orally administered telmisartan for the treatment of systemic hypertension in cats: results of a double-blind, placebo-controlled, randomized clinical trial. J Vet Intern Med 33(2):478–488

    PubMed  PubMed Central  Google Scholar 

  • Conroy M, Chang YM, Brodbelt D, Elliott J (2018) Survival after diagnosis of hypertension in cats attending primary care practice in the United Kingdom. J Vet Intern Med 32(6):1846–1855

    Article  PubMed  PubMed Central  Google Scholar 

  • Ebner T, Schänzle G, Weber W, Sent U, Elliott J (2013) In vitro glucuronidation of the angiotensin II receptor antagonist telmisartan in the cat: a comparison with other species. J Vet Pharmacol Ther 36(2):154–160

    Article  CAS  PubMed  Google Scholar 

  • Edwards LP, Brown-Bryan TA, McLean L, Ernsberger P (2012) Pharmacological properties of the central antihypertensive agent, moxonidine. Cardiovasc Ther 30(4):199–208

    Article  CAS  PubMed  Google Scholar 

  • Elliott J, Barber PJ, Syme HM, Rawlings JM, Markwell PJ (2001) Feline hypertension: clinical findings and response to antihypertensive treatment in 30 cases. J Small Anim Pract 42(3):122–129

    Article  CAS  PubMed  Google Scholar 

  • Elliott J, Fletcher MG, Souttar K, Cariese S, Syme HM (2004) Effect of concomitant amlodipine and benazepril therapy in the management of feline hypertension. J Vet Intern Med 18(5):788 (abstract)

    Google Scholar 

  • EMEA – European Medicines Agency – Veterinary Medicines (2007). https://www.ema.europa.eu/en/documents/scientific-discussion/prilactone-epar-scientific-discussion_en.pdf

  • Farquharson CA, Struthers AD (2000) Spironolactone increases nitric oxide bioactivity, improves endothelial vasodilator dysfunction, and suppresses vascular angiotensin I/angiotensin II conversion in patients with chronic heart failure. Circulation 101(6):594–597

    Article  CAS  PubMed  Google Scholar 

  • Ferrario CM, Mullick AE (2017 Nov) Renin angiotensin aldosterone inhibition in the treatment of cardiovascular disease. Pharmacol Res 125(Pt A):57–71

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Geigy CA, Schweighauser A, Doherr M, Francey T (2011 Jul) Occurrence of systemic hypertension in dogs with acute kidney injury and treatment with amlodipine besylate. J Small Anim Pract 52(7):340–346

    Article  CAS  PubMed  Google Scholar 

  • Glaus TM, Elliott J, Herberich E, Zimmering T, Albrecht B (2019) Efficacy of long-term oral telmisartan treatment in cats with hypertension: results of a prospective European clinical trial. J Vet Intern Med 33(2):413–422

    Article  PubMed  PubMed Central  Google Scholar 

  • Grassi G (2016) Sympathomodulatory effects of antihypertensive drug treatment. Am J Hypertens 29(6):665–675

    Article  CAS  PubMed  Google Scholar 

  • Grassi G, Mark A, Esler M (2015) The sympathetic nervous system alterations in human hypertension. Circ Res 116(6):976–990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grassi G, Robles NR, Seravalle G, Fici F (2017) Lercanidipine in the Management of Hypertension: an update. J Pharmacol Pharmacother 8(4):155–165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grauer GF, Greco DS, Getzy DM, Cowgill LD, Vaden SL, Chew DJ, Polzin DJ, Barsanti JA (2000) Effects of enalapril versus placebo as a treatment for canine idiopathic glomerulonephritis. J Vet Intern Med 14(5):526–533

    Article  CAS  PubMed  Google Scholar 

  • Guyonnet J, Elliott J, Kaltsatos V (2010) A preclinical pharmacokinetic and pharmacodynamic approach to determine a dose of spironolactone for treatment of congestive heart failure in dog. J Vet Pharmacol Ther 33(3):260–267

    Article  CAS  PubMed  Google Scholar 

  • Häggström J, Hansson K, Karlberg BE, Kvart C, Madej A, Olsson K (1996) Effects of long-term treatment with enalapril or hydralazine on the renin-angiotensin-aldosterone system and fluid balance in dogs with naturally acquired mitral valve regurgitation. Am J Vet Res 57(11):1645–1652

    PubMed  Google Scholar 

  • Henik RA, Snyder PS, Volk LM (1997) Treatment of systemic hypertension in cats with amlodipine besylate. J Am Anim Hosp Assoc 33(3):226–234

    Article  CAS  PubMed  Google Scholar 

  • Horiuchi M, Mogi M (2011) Role of angiotensin II receptor subtype activation in cognitive function and ischaemic brain damage. Br J Pharmacol 163(6):1122–1130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huhtinen M, Derré G, Renoldi HJ, Rinkinen M, Adler K, Aspegrén J, Zemirline C, Elliott J (2015) Randomized placebo-controlled clinical trial of a chewable formulation of amlodipine for the treatment of hypertension in client-owned cats. J Vet Intern Med 29(3):786–793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jaisser F, Farman N (2016) Emerging roles of the mineralocorticoid receptor in pathology: toward new paradigms in clinical pharmacology. Pharmacol Rev 68(1):49–75

    Article  CAS  PubMed  Google Scholar 

  • James R, Guillot E, Garelli-Paar C, Huxley J, Grassi V, Cobb M (2018) The SEISICAT study: a pilot study assessing efficacy and safety of spironolactone in cats with congestive heart failure secondary to cardiomyopathy. J Vet Cardiol 20(1):1–12

    Article  PubMed  Google Scholar 

  • Jenkins TL, Coleman AE, Schmiedt CW, Brown SA (2015) Attenuation of the pressor response to exogenous angiotensin by angiotensin receptor blockers and benazepril hydrochloride in clinically normal cats. Am J Vet Res 76(9):807–813

    Article  CAS  PubMed  Google Scholar 

  • Jepson RE, Elliott J, Brodbelt D, Syme HM (2007) Effect of control of systolic blood pressure on survival in cats with systemic hypertension. J Vet Intern Med 21(3):402–409

    Article  PubMed  Google Scholar 

  • Jepson RE, Syme HM, Elliott J (2014) Plasma renin activity and aldosterone concentrations in hypertensive cats with and without azotemia and in response to treatment with amlodipine besylate. J Vet Intern Med 28(1):144–153

    Article  CAS  PubMed  Google Scholar 

  • Jeunesse E, Woehrle F, Schneider M, Lefebvre HP (2007) Effect of spironolactone on diuresis and urine sodium and potassium excretion in healthy dogs. J Vet Cardiol 9(2):63–68

    Article  CAS  PubMed  Google Scholar 

  • King JN, Gunn-Moore DA, Tasker S, Gleadhill A, Strehlau G (2006) Benazepril in renal insufficiency in cats study group. Tolerability and efficacy of benazepril in cats with chronic kidney disease. J Vet Intern Med 20(5):1054–1064

    Article  PubMed  Google Scholar 

  • Kittleson MD, Bonagura JD (2010) Re: Efficacy of spironolactone on survival in dogs with naturally occurring mitral regurgitation caused by myxomatous mitral valve disease. J Vet Intern Med 24(6):1245–1246

    Article  CAS  PubMed  Google Scholar 

  • Lefebvre HP, Toutain PL (2004) Angiotensin-converting enzyme inhibitors in the therapy of renal diseases. J Vet Pharmacol Ther 27(5):265–281

    Article  CAS  PubMed  Google Scholar 

  • Lefebvre HP, Laroute V, Concordet D, Toutain PL (1999) Effects of renal impairment on the disposition of orally administered enalapril, benazepril, and their active metabolites. J Vet Intern Med 13(1):21–27

    Article  CAS  PubMed  Google Scholar 

  • Lefebvre HP, Jeunesse E, Laroute V, Toutain PL (2006) Pharmacokinetic and pharmacodynamic parameters of ramipril and ramiprilat in healthy dogs and dogs with reduced glomerular filtration rate. J Vet Intern Med 20(3):499–507

    Article  PubMed  Google Scholar 

  • Lefebvre HP, Ollivier E, Atkins CE, Combes B, Concordet D, Kaltsatos V, Baduel L (2013) Safety of spironolactone in dogs with chronic heart failure because of degenerative valvular disease: a population-based, longitudinal study. J Vet Intern Med 27(5):1083–1091

    Article  CAS  PubMed  Google Scholar 

  • Lenasi H, Kohlstedt K, Fichtlscherer B, Mülsch A, Busse R, Fleming I (2003) Amlodipine activates the endothelial nitric oxide synthase by altering phosphorylation on Ser1177 and Thr495. Cardiovasc Res 59(4):844–853

    Article  CAS  PubMed  Google Scholar 

  • Lucchesi BR, Tamura Y (1989) Cardioprotective effects of amlodipine in the ischemic-reperfused heart. Am Heart J 118(5 Pt 2):1121–1122

    Article  CAS  PubMed  Google Scholar 

  • MacDonald KA, Kittleson MD, Kass PH, White SD (2008) Effect of spironolactone on diastolic function and left ventricular mass in Maine Coon cats with familial hypertrophic cardiomyopathy. J Vet Intern Med 22(2):335–341

    Article  CAS  PubMed  Google Scholar 

  • Mathur S, Syme H, Brown CA, Elliot J, Moore PA, Newell MA, Munday JS, Cartier LM, Sheldon SE, Brown SA (2002) Effects of the calcium channel antagonist amlodipine in cats with surgically induced hypertensive renal insufficiency. Am J Vet Res 63(6):833–839

    Article  CAS  PubMed  Google Scholar 

  • Mathur S, Brown CA, Dietrich UM, Munday JS, Newell MA, Sheldon SE, Cartier LM, Brown SA (2004) Evaluation of a technique of inducing hypertensive renal insufficiency in cats. Am J Vet Res 65(7):1006–1013

    Article  PubMed  Google Scholar 

  • Mishina M, Watanabe T (2008) Development of hypertension and effects of benazepril hydrochloride in a canine remnant kidney model of chronic renal failure. J Vet Med Sci 70(5):455–460

    Article  CAS  PubMed  Google Scholar 

  • Miura S, Fu**o M, Hanzawa H, Kiya Y, Imaizumi S, Matsuo Y, Tomita S, Uehara Y, Karnik SS, Yanagisawa H, Koike H, Komuro I, Saku K (2006) Molecular mechanism underlying inverse agonist of angiotensin II type 1 receptor. J Biol Chem 281(28):19288–19295

    Article  CAS  PubMed  Google Scholar 

  • Miura S, Karnik SS, Saku K (2011) Review: angiotensin II type 1 receptor blockers: class effects versus molecular effects. J Renin Angiotensin Aldosterone Syst 12(1):1–7

    Article  CAS  PubMed  Google Scholar 

  • Mochel JP, Danhof M (2015) Chronobiology and pharmacologic modulation of the renin-angiotensin-aldosterone system in dogs: what have we learned? Rev Physiol Biochem Pharmacol 169:43–69

    Article  CAS  PubMed  Google Scholar 

  • Mochel JP, Fink M, Peyrou M, Desevaux C, Deurinck M, Giraudel JM, Danhof M (2013) Chronobiology of the renin-angiotensin-aldosterone system in dogs: relation to blood pressure and renal physiology. Chronobiol Int 30(9):1144–1159

    Article  CAS  PubMed  Google Scholar 

  • Mochel JP, Fink M, Bon C, Peyrou M, Bieth B, Desevaux C, Deurinck M, Giraudel JM, Danhof M (2014) Influence of feeding schedules on the chronobiology of renin activity, urinary electrolytes and blood pressure in dogs. Chronobiol Int 31(5):715–730

    Article  CAS  PubMed  Google Scholar 

  • Mochel JP, Fink M, Peyrou M, Soubret A, Giraudel JM, Danhof M (2015) Pharmacokinetic/Pharmacodynamic modeling of renin-angiotensin aldosterone biomarkers following angiotensin-converting enzyme (ACE) inhibition therapy with benazepril in dogs. Pharm Res 32(6):1931–1946

    Article  CAS  PubMed  Google Scholar 

  • Narayan H, Webb DJ (2016) New evidence supporting the use of mineralocorticoid receptor blockers in drug-resistant hypertension. Curr Hypertens Rep 18(5):34

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ojima M, Igata H, Tanaka M, Sakamoto H, Kuroita T, Kohara Y, Kubo K, Fuse H, Imura Y, Kusumoto K, Nagaya H (2011) In vitro antagonistic properties of a new angiotensin type 1 receptor blocker, azilsartan, in receptor binding and function studies. J Pharmacol Exp Ther 336(3):801–808

    Article  CAS  PubMed  Google Scholar 

  • Peterson JC, Alder S, Burkart JM et al (1995) Blood pressure control, proteinuria, and the progression of renal disease. The modification of diet in renal disease study. Ann Intern Med 123:754–762

    Article  CAS  PubMed  Google Scholar 

  • Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J (1999) The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 341(10):709–717

    Article  CAS  PubMed  Google Scholar 

  • Putnam K, Shoemaker R, Yiannikouris F, Cassis LA (2012) The renin-angiotensin system: a target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome. Am J Physiol Heart Circ Physiol 302(6):H1219–H1230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reyes S, Varagic J, Ahmad S, VonCannon J, Kon ND, Wang H, Groban L, Cheng CP, Dell’Italia LJ, Ferrario CM (2017) Novel cardiac Intracrine mechanisms based on Ang-(1-12)/Chymase Axis require a revision of therapeutic approaches in human heart disease. Curr Hypertens Rep 19(2):16

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rosen SG, Supiano MA, Perry TJ, Linares OA, Hogikyan RV, Smith MJ, Halter JB (1990) Beta-adrenergic blockade decreases norepinephrine release in humans. Am J Phys 258(6 Pt 1):E999–E1005

    CAS  Google Scholar 

  • Santos RAS, Sampaio WO, Alzamora AC, Motta-Santos D, Alenina N, Bader M, Campagnole-Santos MJ (2018) The ACE2/angiotensin-(1-7)/MAS Axis of the renin-angiotensin system: focus on angiotensin-(1-7). Physiol Rev 98(1):505–553

    Article  CAS  PubMed  Google Scholar 

  • Sent U, Gössl R, Elliott J, Syme HM, Zimmering T (2015) Comparison of efficacy of long-term oral treatment with telmisartan and benazepril in cats with chronic kidney disease. J Vet Intern Med 29(6):1479–1487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sharma A, Trane A, Yu C, Jasmin JF, Bernatchez P (2011) Amlodipine increases endothelial nitric oxide release by modulating binding of native eNOS protein complex to caveolin-1. Eur J Pharmacol 659(2–3):206–212

    Article  CAS  PubMed  Google Scholar 

  • Snyder PS (1998) Amlodipine: a randomized, blinded clinical trial in 9 cats with systemic hypertension. J Vet Intern Med 12(3):157–162

    Article  CAS  PubMed  Google Scholar 

  • Syme HM, Barber PJ, Markwell PJ, Elliott J (2002) Prevalence of systolic hypertension in cats with chronic renal failure at initial evaluation. J Am Vet Med Assoc 220(12):1799–1804

    Article  PubMed  Google Scholar 

  • Takezako T, Unal H, Karnik SS, Node K (2017) Current topics in angiotensin II type 1 receptor research: focus on inverse agonism, receptor dimerization and biased agonism. Pharmacol Res 123:40–50

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Toma L, Stancu CS, Sanda GM, Sima AV (2011) Anti-oxidant and anti-inflammatory mechanisms of amlodipine action to improve endothelial cell dysfunction induced by irreversibly glycated LDL. Biochem Biophys Res Commun 411(1):202–207

    Article  CAS  PubMed  Google Scholar 

  • Toutain PL, Lefebvre HP (2004) Pharmacokinetics and pharmacokinetic/pharmacodynamic relationships for angiotensin-converting enzyme inhibitors. J Vet Pharmacol Ther 27(6):515–525

    Article  CAS  PubMed  Google Scholar 

  • Toutain PL, Lefebvre HP, King JN (2000) Benazeprilat disposition and effect in dogs revisited with a pharmacokinetic/pharmacodynamic modeling approach. J Pharmacol Exp Ther 292(3):1087–1093

    CAS  PubMed  Google Scholar 

  • Towfighi A, Ovbiagele B (2008) Partial peroxisome proliferator-activated receptor agonist angiotensin receptor blockers. Potential multipronged strategy in stroke prevention. Cerebrovasc Dis 26(2):106–112

    Article  CAS  PubMed  Google Scholar 

  • Vongpatanasin W, Kario K, Atlas SA, Victor RG (2011) Central sympatholytic drugs. J Clin Hypertens (Greenwich) 13(9):658–661

    Article  CAS  Google Scholar 

  • Wang W (1994) Chronic administration of aldosterone depresses baroreceptor reflex function in the dog. Hypertension 24(5):571–575

    Article  CAS  PubMed  Google Scholar 

  • Yao K, Nagashima K, Miki H (2006) Pharmacological, pharmacokinetic, and clinical properties of benidipine hydrochloride, a novel, long-acting calcium channel blocker. J Pharmacol Sci 100(4):243–261

    Article  CAS  PubMed  Google Scholar 

  • Yasuda N, Miura S, Akazawa H, Tanaka T, Qin Y, Kiya Y, Imaizumi S, Fu**o M, Ito K, Zou Y, Fukuhara S, Kunimoto S, Fukuzaki K, Sato T, Ge J, Mochizuki N, Nakaya H, Saku K, Komuro I (2008) Conformational switch of angiotensin II type 1 receptor underlying mechanical stress-induced activation. EMBO Rep 9(2):179–186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zannad F, Alla F, Dousset B, Perez A, Pitt B (2000) Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the randomized aldactone evaluation study (RALES). Rales Investigators. Circulation 102(22):2700–2706

    Article  CAS  PubMed  Google Scholar 

  • Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J, Pocock SJ, Pitt B, EMPHASIS-HF Study Group (2011) Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 364(1):11–21

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Hintze TH (1998) Amlodipine releases nitric oxide from canine coronary microvessels: an unexpected mechanism of action of a calcium channel-blocking agent. Circulation 97(6):576–580

    Article  CAS  PubMed  Google Scholar 

  • Zou Y, Akazawa H, Qin Y, Sano M, Takano H, Minamino T, Makita N, Iwanaga K, Zhu W, Kudoh S, Toko H, Tamura K, Kihara M, Nagai T, Fukamizu A, Umemura S, Iiri T, Fujita T, Komuro I (2004) Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II. Nat Cell Biol 6(6):499–506

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Comparative Biomedical Sciences, Royal Veterinary College, University of London, London, UK

    Jonathan Elliott & Ludovic Pelligand

Authors
  1. Jonathan Elliott
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ludovic Pelligand
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jonathan Elliott .

Editor information

Editors and Affiliations

  1. Department of Comparative Biomedical Sciences, Royal Veterinary College University of London, London, UK

    Jonathan Elliott

  2. Department of Clinical Sciences and Services, Royal Veterinary College University of London, Hertfordshire, UK

    Harriet M. Syme

  3. Department of Clinical Sciences and Services, Royal Veterinary College University of London, Hertfordshire, UK

    Rosanne E. Jepson

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Elliott, J., Pelligand, L. (2020). Pharmacology of Antihypertensive Drugs. In: Elliott, J., Syme, H., Jepson, R. (eds) Hypertension in the Dog and Cat. Springer, Cham. https://doi.org/10.1007/978-3-030-33020-0_11

Download citation

Publish with us

Policies and ethics

Search

Navigation