These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Antihypertensive therapy augments endothelium-dependent relaxations in coronary arteries of spontaneously hypertensive rats.
    Author: Tschudi MR, Criscione L, Novosel D, Pfeiffer K, Lüscher TF.
    Journal: Circulation; 1994 May; 89(5):2212-8. PubMed ID: 8181147.
    Abstract:
    BACKGROUND: Coronary artery disease is an important complication of hypertension. Therefore, the effects of antihypertensive therapy on the endothelial nitric oxide (NO)/L-arginine pathway and vascular smooth muscle were studied in left anterior descending coronary arteries of Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Angiotensin II (AT1) receptor antagonists CGP 48369 and valsartan, angiotensin-converting enzyme inhibitor benazepril HCl, and calcium antagonist nifedipine were used as antihypertensive agents. METHODS AND RESULTS: Rings were examined in myograph systems for isometric tension recording. In untreated WKY and SHR rings, acetylcholine (10(-9) to 10(-5) mol/L) but not bradykinin, substance P (both 10(-6) mol/L), or thrombin (1 U/mL) induced comparable endothelium-dependent relaxations. These relaxations were markedly decreased by NG-monomethyl-L-arginine (10(-4) mol/L) and fully prevented by N omega-nitro-L-arginine methyl ester (10(-4) mol/L) or methylene blue (10(-5) mol/L). In vitro treatment of WKY and SHR rings with benazeprilat, CGP 48369, or valsartan (3 x 10(-7) mol/L) did not affect responses to acetylcholine. In SHR, chronic therapy for 8 weeks with benazepril HCl, CGP 48369, valsartan, or nifedipine (each 10 mg.kg-1.d-1 PO) similarly reduced blood pressure and increased endothelium-dependent relaxations to acetylcholine (log shift at IC50, ie, half-maximal inhibition of a preceding contraction, 10-, 8-, 13-, and 13-fold, P < .05 versus control), whereas relaxations to the NO donor 3-morpholino sydnonimine (SIN-1, 10(-9) to 10(-5) mol/L) remained unaffected. In WKY, chronic therapy with nifedipine (10 mg.kg-1.d-1 PO) affected neither blood pressure nor relaxations to acetylcholine or SIN-1. CONCLUSIONS: In rat coronary arteries, NO is synthesized via the endothelial L-arginine pathway and released after stimulation with acetylcholine. In SHR, chronic antihypertensive therapy with either angiotensin receptor antagonists, an angiotensin-converting enzyme inhibitor, or a calcium antagonist specifically increased the normal endothelium-dependent relaxations to acetylcholine, probably because of their blood pressure-lowering effects, whereas the responsiveness of vascular smooth muscle to NO remained unaffected.
    [Abstract] [Full Text] [Related] [New Search]