CARDIOVASCULAR PROPERTIES OF ANTIHYPERTENSIVE DRUGS IN A MODEL OF SEVERE RENAL-HYPERTENSION

Various experimental models are available for characterizing the antihypertensive properties of drugs. Although advantages are claimed for each, an ideal model has not yet emerged. An examination of the antihypertensive properties of 5 classes of antihypertensive drugs was made in a model of malignant hypertension. In rats made severely hypertensive by aortic coarctation, centrally acting drugs (clonidine and methyldopa) and peripheral vasodilators (hydralazine and minoxidil) produced a greater decrease in mean arterial pressure than did βadrenergic blockers (propranolol and timolol), inhibitors of the renin-angiotensin system (Sar1,lle8-Angiotensin II, SQ 20881, SQ 14225), and saluretics (hydrochlorothiazide and MK-447). In comparison to spontaneously hypertensive rats, the antihypertensive properties of β-adrenoceptor antagonists and saluretics were readily shown in rats with malignant hypertension. Chronic administration of methyldopa, but not propranolol, attenuated the development of hypertension in this model. The antihypertensive response to an intracerebroventricular injection of clonidine in these renal hypertensive rats was significantly depressed compared to spontaneously hypertensive rats with comparable blood pressures. In addition, the hind-limb vasoconstrictor responses to norepinephrine and angiotensin II were attenuated in the perfused hindquarters of hypertensive rats compared to sham rats. These results suggest that the antihypertensive properties of a variety of drugs can be characterized in rats made hypertensive by aortic coarctation and that mechanism of action studies based on direct central injections and changes in hindquarter hemodynamics can be made in these animals. © 1979.