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Ramipril therapy improves arterial dilation in experimental hypertension
N Hutri-Kähönen1, M Kähönen, J P Tolvanen
1Medical School, University of Tampere, Finland.
Cardiovascular Research
|January 1, 1997
Summary
Ramipril therapy normalized blood pressure and improved blood vessel dilation in spontaneously hypertensive rats. This enhanced relaxation is linked to reduced constricting factors and better endothelium-dependent hyperpolarization.
Area of Science:
- Cardiovascular Pharmacology
- Hypertension Research
- Endothelial Function Studies
Background:
- Endothelial dysfunction is a hallmark of hypertension.
- Angiotensin-converting enzyme (ACE) inhibitors can restore endothelial function.
- The specific mechanisms underlying enhanced endothelium-dependent dilation require further elucidation.
Purpose of the Study:
- To investigate the effects of long-term ACE inhibition with ramipril on endothelial function in spontaneously hypertensive rats (SHR).
- To characterize the roles of nitric oxide (NO) and prostanoids in the enhanced vasodilation observed after ramipril treatment.
- To explore the contribution of K+ channels to endothelium-dependent hyperpolarization.
Main Methods:
- In vitro study of mesenteric arterial rings from SHR and Wistar-Kyoto rats (WKY).
- Administration of ramipril (1 mg.kg-1.day-1) for 12 weeks.
- Assessment of relaxation responses to acetylcholine (ACh) and isoprenaline, with and without inhibitors of cyclo-oxygenase (diclofenac) and NO synthase (L-NAME).
- Evaluation of endothelium-dependent hyperpolarization by precontracting with potassium chloride (KCl) and using K+ channel blockers (glibenclamide, apamin).
Main Results:
- Ramipril treatment significantly reduced blood pressure in SHR.
- Endothelium-dependent relaxations to ACh were enhanced in ramipril-treated SHR compared to untreated SHR.
- Diclofenac enhanced ACh-induced relaxation in untreated SHR, while L-NAME attenuated it more in untreated SHR, suggesting roles for both prostanoids and NO.
- Ramipril therapy augmented endothelium-dependent hyperpolarization, indicated by preserved ACh-induced relaxation when NO and prostanoid pathways were inhibited, and further modulated by K+ channel blockers.
Conclusions:
- Long-term ramipril therapy effectively lowers blood pressure and improves arterial dilation in experimental hypertension.
- Enhanced endothelium-mediated relaxation post-ramipril is attributed to decreased synthesis of vasoconstrictive prostanoids and improved endothelium-dependent hyperpolarization.
- These findings highlight the multifaceted mechanisms through which ACE inhibition benefits vascular function in hypertension.