title: Arterial function in mineralocorticoid-NaCl hypertension: influence of angiotensin-converting enzyme inhibition.
abstract: Angiotensin-converting enzyme inhibitors have been suggested to improve the function of arterial endothelium and smooth muscle not only through inhibition of angiotensin II formation and reduction of blood pressure, but also via additional pathways, e.g. potentiation of endogenous kinins and enhancement of endothelial autacoid formation. Therefore, we investigated whether 10-week-long quinapril therapy (10 mg kg-1 day-1) 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 cardiac hypertrophy in deoxycorticosterone-NaCl hypertension. In noradrenaline-precontracted arterial rings the endothelium-dependent relaxations to acetylcholine and adenosine 5'-diphosphate as well as the endothelium-independent relaxations to nitroprusside and isoprenaline were clearly 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 inhibitor NG-nitro-L-arginine methyl ester, the relaxations to acetylcholine in untreated and quinapril-treated hypertensive animals were practically absent, whereas in normotensive rats distinct relaxations to higher concentrations of acetylcholine were still present. Interestingly, when endothelium-dependent hyperpolarization was prevented by precontracting the preparations with potassium chloride, no differences were found in relaxations to acetylcholine and adenosine 5'-diphosphate between the study groups. Exogenous bradykinin induced small comparable contractions in endothelium-intact mesenteric arterial rings from all study groups. In conclusion, the 10-week-long quinapril therapy did not have any significant effects on arterial function in deoxycorticosterone-NaCl hypertensive rats. Therefore, the present results stress the roles of reduced blood pressure and diminished angiotensin II formation in the beneficial vascular effects of long-term angiotensin-converting enzyme inhibition in the present model of hypertension. Furthermore, since the relaxations to acetylcholine and adenosine 5'-diphosphate in the deoxycorticosterone-NaCl-treated rats were attenuated in the absence and presence of nitric oxide synthase inhibition but not under conditions which prevented hyperpolarization, impaired endothelium-dependent relaxation to agonists can be attributed to diminished endothelium-dependent hyperpolarization in this model of hypertension.
authors.affiliation: Medical School, University of Tampere, Finland.
authors.forename: H
authors.initials: H
authors.lastname: Mäkynen
authors.forename: M
authors.initials: M
authors.lastname: Kähönen
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.forename: N
authors.initials: N
authors.lastname: Hutri-Kähönen
authors.forename: J P
authors.initials: JP
authors.lastname: Tolvanen
authors.forename: I
authors.initials: I
authors.lastname: Pörsti
mesh_terms: D000109:Acetylcholine; D000804:Angiotensin II / Q000096:biosynthesis; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003900:Desoxycorticosterone / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy*; D007546:Isoquinolines / Q000627:therapeutic use*; D008297:Male; D008638:Mesenteric Arteries; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D000077583:Quinapril; D051381:Rats; D011921:Rats, Inbred WKY; D012965:Sodium Chloride / Q000008:administration & dosage; D044005:Tetrahydroisoquinolines
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D000804:Angiotensin II; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D000077583:Quinapril; D019331:NG-Nitroarginine Methyl Ester