Effects of cilazapril on cerebral vasodilatation in hypertensive rats.
Endothelium-dependent dilatation of cerebral arterioles is impaired during chronic hypertension. The goal of this study was to determine the effects of an angiotensin converting enzyme inhibitor, cilazapril, on endothelium-dependent dilatation in pial arterioles. Four-month-old Wistar-Kyoto (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP) received cilazapril in their drinking water (500 mg/L) for 3 to 6 months. Treatment with cilazapril reduced mean arterial pressure in both WKY rats and SHRSP and had no significant effect on baseline diameter of pial arterioles measured with a cranial window. Responses to bradykinin and A23187, but not to nitroglycerin and adenosine, were impaired in SHRSP. Cilazapril did not affect responses to bradykinin (3 x 10(-7) M) and A23187 (10(-5) M) in WKY rats but significantly increased cerebral vasodilatation in response to bradykinin (52 +/- 4% vs 27 +/- 5%) and A23187 (19 +/- 3% vs 8 +/- 3%) in SHRSP. Cilazapril also tended to increase dilator responses to nitroglycerin and adenosine in SHRSP. In another group of SHRSP, treatment with cilazapril for 4 days produced a moderate reduction in blood pressure and increased cerebral vasodilatation in response to bradykinin, A23187, and adenosine. Topical application of the active form of cilazapril (cilazaprilat) for 40 minutes also increased cerebral vasodilatation in response to bradykinin, A23187, and nitroglycerin in SHRSP. The data indicate that an angiotensin converting enzyme inhibitor enhances cerebral vasodilatation in response to endothelium-dependent agonists in SHRSP and may also increase responses to endothelium-independent agonists.
Yang
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Department of Pharmacology, University of Iowa College of Medicine, Iowa City 52242.
Faraci
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Heistad
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D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D017315:Cilazapril / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D017315:Cilazapril; D000001:Calcimycin; D001920:Bradykinin