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Effects of cilazapril on cerebral vasodilatation in hypertensive rats
S T Yang1, F M Faraci, D D Heistad
1Department of Pharmacology, University of Iowa College of Medicine, Iowa City 52242.
Insights
Angiotensin converting enzyme inhibitors like cilazapril improve cerebral blood vessel function in hypertensive rats. This treatment enhances endothelium-dependent vasodilation, crucial for healthy brain blood flow.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Cerebrovascular Research
Background:
- Chronic hypertension impairs endothelium-dependent dilatation of cerebral arterioles.
- Understanding interventions to restore cerebral vascular function is critical.
Purpose of the Study:
- To investigate the effects of cilazapril, an angiotensin converting enzyme inhibitor, on endothelium-dependent dilatation in pial arterioles.
- To assess cilazapril's impact on cerebral vasodilatation in both normotensive and hypertensive rat models.
Main Methods:
- Wistar-Kyoto (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP) were treated with cilazapril in drinking water for 3-6 months.
- Cerebral arteriole responses to vasodilators (bradykinin, A23187, nitroglycerin, adenosine) were measured using a cranial window.
- Short-term (4-day) and topical (cilazaprilat) administration were also evaluated in SHRSP.
Main Results:
- Cilazapril reduced mean arterial pressure in both WKY and SHRSP rats.
- Endothelium-dependent vasodilatation to bradykinin and A23187 was significantly enhanced by cilazapril in SHRSP.
- Cilazapril tended to improve responses to nitroglycerin and adenosine in SHRSP, suggesting broader vascular effects.
Conclusions:
- Angiotensin converting enzyme inhibition with cilazapril enhances cerebral vasodilatation in response to endothelium-dependent agonists in hypertensive rats.
- Cilazapril may also improve responses to endothelium-independent agonists, offering potential therapeutic benefits for hypertension-related cerebrovascular dysfunction.
Abstract:
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.