7/31/2019 Drogas de Renoptoteccion

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Proceeding of the NAVC

North American Veterinary ConferenceJan. 8-12, 2005, Orlando, Florida

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7/31/2019 Drogas de Renoptoteccion

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Small Animal Nephrology Nephrology - Urology

519

VASOACTIVE DRUGS:

CONTROVERSIES IN RENOPROTECTION

Scott A. Brown, VMD, PhD, Diplomate ACVIMCollege of Veterinary Medicine

University of Georgia, Athens, GA

Systemic hypertension is often present in dogs and catswith renal failure and this high blood pressure can produce

intrarenal injury leading to a self-perpetuating cycle of kidneydisease leading to systemic hypertension contributing tofurther renal damage, etc.

THE ROLE OF THE RENAL ARTERIOLES

In the normal kidney, the afferent arteriole maintainsconstancy of kidney functions (e.g., GFR, renal blood flow,and glomerular capillary pressure) through reflexvasoconstriction or vasodilation. If systemic arterial bloodpressure rises above normal (i.e., during systemichypertension) the afferent arteriole constricts to maintainpressures and flows within the kidney. Further, the efferentarteriole can act as a pressure relief valve throughvasodilation, which leads to a fall in glomerular capillary

pressure or vasoconstriction which can facilitate a rise inglomerular capillary pressure. Collectively, this capacity ofthe renal arterioles is referred to as renal autoregulation.

EFFECTS OF KIDNEY DISEASE ON ARTERIOLAR

FUNCTION

In dogs and cats with kidney disease, the afferent arterioleis stuck open in an effort to raise GFR and thiscompromises autoregulatory function. Thus, if an animal withkidney disease develops systemic hypertension, this increasein upstream pressure in the arterial tree will be transmittedinto the glomerulus. Thus, dogs and cats with chronic kidneydisease tend to experience high pressures within theglomerular capillary bed, referred to as glomerular

hypertension. This is deleterious to kidney structure andfunction and ultimately causes progressive renal injury.

THE IDEAL ANTIHYPERTENSIVE AGENT?

This scenario has led to the concept that the idealantihypertensive agent should lower systemic arterial bloodpressure and also protect the kidney from further injury,referred to as renoprotection. Two types of vasodilatoryagents have proven renoprotective effects in rodents andpeople with kidney disease: angiotensin converting enzymeinhibitors (ACEI) and calcium channel blockers (CCB).

The ACEI inhibit the formation of angiotensin II which is apotent vasoconstrictor, of the efferent arteriole. An ACE(e.g., benazepril or enalapril) will often lower systemic arteriablood pressure through systemic vasodilation. The ACEalso tend to lower intraglomerular pressure by producingselective efferent arteriolar vasodilation (open the pressurerelief valve). The ACEI have other non-hemodynamiceffects, such as interference with renal fibrogenesis.

The CCB (e.g., amlodipine) cause vasodilation which tends

to reduce total peripheral resistance and systemic arteriablood pressure. Unfortunately, the commonly used CCBpreferentially dilate the afferent arteriole. By itself, this wiltend to raise intraglomerular pressure and could actuallypromote intrarenal hypertension and barotrauma. Howeverthe net effect of reducing the upstream pressure (systemicarterial pressure) coupled with afferent arteriolar vasodilationis hard to predict. Further, the CCB have nonhemodynamiceffects that may offer renoprotection. Currently, because otheir very good effects of CCB in lowering systemic arteriablood pressure and ACEI in lowering intraglomerulapressure, the co-administration of CCB and ACEI is in favor.

REFERENCES

1. Brown SA, Finco DR, Crowell WA, et al. Single-nephronadaptations to partial renal ablation in the dog. Am JPhysiol1990;258:495-503.

2. Brown SA, Walton CL, Crawford P, et al. Long-termeffects of antihypertensive regimens on renahemodynamics and proteinuria. Kidney In1993;43:1210-1218.

3. Brown S, Finco D, Navar L. Impaired renaautoregulatory ability in dogs with reduced renal mass. JAm Soc Nephr1995;5:1168-1174.

4. Brown SA, Brown CA. Single-nephron adaptations topartial renal ablation in cats. Am J Physio1996;269:R1002-R1008.

5. Brown S, Brown C, Hendi R. Does systemic

hypertension damage the canine kidney? ProceedingsAm Coll Vet Int Med 2000, Seattle, 728A.

6. Elliott J, Barber PJ, Syme HM, Rawlings JM, MarkwelPJ. Feline hypertension: clinical findings and response toantihypertensive treatment in 30 cases. J Small AnimPract2001;42:122-129.

7. Jensen J, Henik RA, Brownfield M, et al. Plasma reninactivity, angiotensin I and aldosterone in felinehypertension associated with chronic renal disease. AmJ Vet Res1997;58:535-540.

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