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Proceeding of the NAVC North American Veterinary Conference

Jan. 8-12, 2005, Orlando, Florida

Reprinted in the IVIS website with the permission of the NAVC http://www.ivis.org/

Published in IVIS with the permission of the NAVC

Small Animal Nephrology Nephrology - Urology

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VASOACTIVE DRUGS: CONTROVERSIES IN RENOPROTECTION

Scott A. Brown, VMD, PhD, Diplomate ACVIM College of Veterinary Medicine University of Georgia, Athens, GA Systemic hypertension is often present in dogs and cats with renal failure and this high blood pressure can produce intrarenal injury leading to a self-perpetuating cycle of kidney disease leading to systemic hypertension contributing to further renal damage, etc. THE ROLE OF THE RENAL ARTERIOLES In the normal kidney, the afferent arteriole maintains constancy of kidney functions (e.g., GFR, renal blood flow, and glomerular capillary pressure) through reflex vasoconstriction or vasodilation. If systemic arterial blood pressure rises above normal (i.e., during systemic hypertension) the afferent arteriole constricts to maintain pressures and flows within the kidney. Further, the efferent arteriole can act as a pressure relief valve through vasodilation, which leads to a fall in glomerular capillary pressure or vasoconstriction which can facilitate a rise in glomerular capillary pressure. Collectively, this capacity of the renal arterioles is referred to as renal autoregulation. EFFECTS OF KIDNEY DISEASE ON ARTERIOLAR FUNCTION In dogs and cats with kidney disease, the afferent arteriole is stuck open in an effort to raise GFR and this compromises autoregulatory function. Thus, if an animal with kidney disease develops systemic hypertension, this increase in upstream pressure in the arterial tree will be transmitted into the glomerulus. Thus, dogs and cats with chronic kidney disease tend to experience high pressures within the glomerular capillary bed, referred to as glomerular hypertension. This is deleterious to kidney structure and function and ultimately causes progressive renal injury. THE IDEAL ANTIHYPERTENSIVE AGENT? This scenario has led to the concept that the ideal antihypertensive agent should lower systemic arterial blood pressure and also protect the kidney from further injury, referred to as renoprotection. Two types of vasodilatory agents have proven renoprotective effects in rodents and people with kidney disease: angiotensin converting enzyme inhibitors (ACEI) and calcium channel blockers (CCB).

The ACEI inhibit the formation of angiotensin II which is a potent vasoconstrictor, of the efferent arteriole. An ACEI (e.g., benazepril or enalapril) will often lower systemic arterial blood pressure through systemic vasodilation. The ACEI also tend to lower intraglomerular pressure by producing selective efferent arteriolar vasodilation (open the pressure relief valve). The ACEI have other non-hemodynamic effects, such as interference with renal fibrogenesis. The CCB (e.g., amlodipine) cause vasodilation which tends to reduce total peripheral resistance and systemic arterial blood pressure. Unfortunately, the commonly used CCB preferentially dilate the afferent arteriole. By itself, this will tend to raise intraglomerular pressure and could actually promote intrarenal hypertension and barotrauma. However, the net effect of reducing the upstream pressure (systemic arterial pressure) coupled with afferent arteriolar vasodilation is hard to predict. Further, the CCB have nonhemodynamic effects that may offer renoprotection. Currently, because of their very good effects of CCB in lowering systemic arterial blood pressure and ACEI in lowering intraglomerular pressure, the co-administration of CCB and ACEI is in favor. REFERENCES

1. Brown SA, Finco DR, Crowell WA, et al. Single-nephron 2.

adaptations to partial renal ablation in the dog. Am J Physiol 1990;258:495-503. Brown SA, Walton CL, Crawford P, et al. Long-term effects of antihypertensive regimens on renal hemodynamics and proteinuria. Kidney Int 1993;43:1210-1218. Brown S, Finco D, Navar L. Impaired renal autoregulatory ability in dogs with reduced renal mass. J Am Soc Nephr 1995;5:1168-1174. Brown SA, Brown CA. Single-nephron adaptations to partial renal ablation in cats. Am J Physiol 1996;269:R1002-R1008. Brown S, Brown C, Hendi R. Does systemic hypertension damage the canine kidney? Proceedings, Am Coll Vet Int Med 2000, Seattle, 728A. Elliott J, Barber PJ, Syme HM, Rawlings JM, Markwell PJ. Feline hypertension: clinical findings and response to antihypertensive treatment in 30 cases. J Small Anim Pract 2001;42:122-129. Jensen J, Henik RA, Brownfield M, et al. Plasma renin activity, angiotensin I and aldosterone in feline hypertension associated with chronic renal disease. Am J Vet Res 1997;58:535-540.

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