Comparative effects of candesartan and enalapril on augmented vasoconstrictive responses to endothelin-1 in coronary vessels of spontaneously hypertensive rats

• Published in: American journal of hypertension Vol. 15; no. 3; pp. 286 - 290
• Main Authors: Miki, Shigeyuki, Takeda, Kazuo, Hatta, Tsuguru, Harada, Sanae, Kido, Hidenori, Oguni, Atsushi, Moriguchi, Jiro, Morimoto, Satoshi, Kawa, Tetsuyoshi, Sasaki, Susumu, Nakagawa, Masao
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.03.2002; Oxford University Press; Elsevier Science
• Subjects: ACE inhibitor; AII antagonist; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Antihypertensive agents; Benzimidazoles - pharmacology; Biological and medical sciences; Blood Pressure - drug effects; Cardiomegaly - prevention & control; Cardiovascular system; coronary circulation; Coronary Vessels - drug effects; Coronary Vessels - physiopathology; Dose-Response Relationship, Drug; Enalapril - pharmacology; endothelin-1; Endothelin-1 - pharmacology; Hypertension - physiopathology; hypertensive hearts; In Vitro Techniques; Medical sciences; Pharmacology. Drug treatments; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Tetrazoles - pharmacology; Vascular Resistance - drug effects; Vasoconstriction - drug effects; Vasoconstriction - physiology; coronary circulation; hypertensive hearts; AII antagonist; endothelin-1; ACE inhibitor; Pharmacologic test; Rat; Candesartan; Peptide hormone; Cardiovascular disease; Vasomotricity; Enalapril; Vasoconstrictor agent; Angiotensin II; Hypertension; Cilexetil; Treatment efficiency; Rodentia; Exploration; Endothelin 1; Angiotensin receptor; Coronary vessel; Genetic disease; Vertebrata; Chemotherapy; Mammalia; Treatment; Benzimidazole derivatives; Biphenyl derivatives; Animal; Antihypertensive agent; Angiotensin antagonist; Hemodynamics; Comparative study
• ISSN: 0895-7061; 1879-1905; 1941-7225
• DOI: 10.1016/S0895-7061(01)02325-1

The aim of this study was to compare the effect of angiotensin type-1 receptor blockade (ARB) on augmented vasoconstrictive response to endothelin-1 (ET-1) in coronary vessels of hypertensive hearts with angiotensin converting enzyme (ACE) inhibitor, candesartan cilexetil (CAN) or enalapril was administered for 3 weeks in spontaneously hypertensive rats (SHR). We used SHR (9 to 12 weeks old, n = 18) and Wistar-Kyoto (WKY) rats ( n = 6). Systolic blood pressure was measured once a week. Spontaneously hypertensive rats were divided into three groups. Enalapril malate (10 mg/day) or CAN (10 mg/day) was administered orally in each of six SHR in each group receiving treatment for 3 weeks. The control group ( n = 6) received no treatment. At the end of this experiment, the hearts were isolated. Isolated hearts mounted on a Langendorff apparatus after weighing were then perfused with modified Krebs-Henseleit buffer at constant pressure (75 mm Hg). The coronary perfusion pressure and coronary flow were measured during perfusion of isolated hearts. Coronary vascular resistance (CVR; mm Hg/mL/min/100 g) was calculated. The ET-1 elicited increases in CVR dose-dependently in both normotensive and hypertensive rat hearts. However, the responses were significantly greater in SHR than in WKY rat. Chronic treatment with enalapril or candesartan inhibited the development of hypertension and cardiac hypertrophy equally in SHR. Augmented vasoconstrictive responses to ET-1 were significantly reduced in treated SHR. There was no difference in these effects between enalapril and candesartan. These findings suggest that both ACE inhibitors and ARB can equally inhibit augmented coronary vascular response to ET-1 in hypertensive hearts.