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


METHODS
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.


RESULTS
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.


CONCLUSIONS
These findings suggest that both ACE inhibitors and ARB can equally inhibit augmented coronary vascular response to ET-1 in hypertensive hearts.
Miki
Shigeyuki
S
Second Department of Medicine, Kyoto Prefectural University of Medicine, Japan. takeda@koto.kpu-m.ac.jp
Takeda
Kazuo
K
Hatta
Tsuguru
T
Harada
Sanae
S
Kido
Hidenori
H
Oguni
Atsushi
A
Moriguchi
Jiro
J
Morimoto
Satoshi
S
Kawa
Tetsuyoshi
T
Sasaki
Susumu
S
Nakagawa
Masao
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000517:prevention & control; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000494:pharmacology*; D019332:Endothelin-1 / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013777:Tetrazoles / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D019332:Endothelin-1; D013777:Tetrazoles; D004656:Enalapril; C081643:candesartan