H. Makynen et al., ARTERIAL FUNCTION IN MINERALOCORTICOID-NACL HYPERTENSION - INFLUENCE OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITION, Pharmacology & toxicology, 81(4), 1997, pp. 180-189
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.