ARTERIAL FUNCTION IN MINERALOCORTICOID-NACL HYPERTENSION - INFLUENCE OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITION

Angiotensin-converting enzyme inhibitors have been suggested to improv e the function of arterial endothelium and smooth muscle not only thro ugh inhibition of angiotensin II formation and reduction of blood pres sure, but also via additional pathways, e.g. potentiation of endogenou s kinins and enhancement of endothelial autacoid formation. Therefore, we investigated whether 10-week-long quinapril therapy (10 mg kg-L da y-L) could beneficially influence the function of mesenteric arterial rings in vitro in deoxycorticosterone-NaCl-treated Wistar-Kyoto rats, a model of hypertension which is known to be resistant to angiotensin- converting enzyme inhibition. The quinapril treatment had no long-term blood pressure-lowering effect nor did it reduce the associated cardi ac hypertrophy in deoxycorticosterone-NaCl hypertension. In noradrenal ine-precontracted arterial rings the endothelium-dependent relaxations to acetylcholine and adenosine 5'-diphosphate as well as the endothel ium-independent relaxations to nitroprusside and isoprenaline were cle arly attenuated in the deoxycorticosterone-NaCl-treated rats. However, the quinapril therapy was without significant effect on any of these dilatory responses. In the presence of the nitric oxide synthase inhib itor NG-nitro-L-arginine methyl ester, the relaxations to acetylcholin e in untreated and quinapril-treated hypertensive animals were practic ally absent, whereas in normotensive rats distinct relaxations to high er concentrations of acetylcholine were still present. Interestingly, when endothelium-dependent hyperpolarization was prevented by precontr acting the preparations with potassium chloride, no differences were f ound in relaxations to acetylcholine and adenosine 5'-diphosphate betw een the study groups. Exogenous bradykinin induced small comparable co ntractions in endothelium-intact mesenteric arterial rings from all st udy groups. In conclusion, the 10-week-long quinapril therapy did not have any significant effects on arterial function in deoxycorticostero ne-NaCl hypertensive rats. Therefore, the present results stress the r oles of reduced blood pressure and diminished angiotensin II formation in the beneficial vascular effects of long-term angiotensin-convertin g enzyme inhibition in the present model of hypertension. Furthermore, since the relaxations to acetylcholine and adenosine 5'-diphosphate i n the deoxycorticosterone-NaCl-treated rats were attenuated in the abs ence and presence of nitric oxide synthase inhibition but not under co nditions which prevented hyperpolarization, impaired endothelium-depen dent relaxation to agonists can be attributed to diminished endotheliu m-dependent hyperpolarization in this model of hypertension.