Antihypertensive treatment improves endothelium-dependent hyperpolarization in the mesenteric artery of spontaneously hypertensive rats.
BACKGROUND
The vascular endothelium releases endothelium-derived hyperpolarizing factor (EDHF). The mesenteric arteries of 6- to 8-month-old spontaneously hypertensive rats (SHRs) exhibit an impairment of the hyperpolarization induced by acetylcholine via EDHF.


RESULTS
We determined whether antihypertensive treatment can improve EDHF-mediated responses in SHRs. Beginning at age 8 to 9 months, the animals were treated with either enalapril (40 mg x kg(-1) x d(-1)) (SHR-Es) or a combination of hydralazine (25 mg x kg(-1) x d(-1)) and hydrochlorothiazide (7.5 mg x kg(-1) x d(-1)) (SHR-Hs) for 3 months. The control groups were age-matched SHRs (SHR-Cs) and Wistar Kyoto rats (WKYs). The two treatments lowered the blood pressure to comparable extents. The acetylcholine-induced hyperpolarization in the mesenteric artery of treated SHRs improved to a level comparable to that in WKYs (acetylcholine 10(-5) mol/L with norepinephrine 10(-5) mol/L: SHR-E, -14.4 +/- 1.8; SHR-H, -12.0 +/- 1.3; SHR-C, -7.2 +/- 1.2; and WKY, -13.3 +/- 2.3 mV). EDHF-mediated relaxation, as assessed by relaxation to acetylcholine resistant to N(G)-nitro-L-arginine in norepinephrine-contracted rings, was markedly improved in treated SHRs (maximal relaxation: SHR-E, 79.3+/-3.2%; SHR-H, 47.4+/-8.6%; SHR-C, 4.8+/-2.4%; and WKY, 45.1+/-6.0%). When the rings were contracted with 77 mmol/L KCl to eliminate EDHF response, no difference was found in relaxation to acetylcholine among the four groups. Similarly, the hyperpolarization and relaxation to levcromakalim, a K+ channel opener, were comparable among the groups.


CONCLUSIONS
Antihypertensive treatment improved EDHF-mediated hyperpolarization and relaxation in the mesenteric artery in SHRs, whereas NO-mediated relaxation did not appear to be modulated by drug therapy. Thus, alterations in the EDHF system may play a pivotal role in endothelial dysfunction and its improvement with drug therapy in SHRs.
Onaka
U
U
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan. uran@mailserver.med.kyushu-u.ac.jp
Fujii
K
K
Abe
I
I
Fujishima
M
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002216:Captopril / Q000494:pharmacology; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000503:physiopathology*; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology; D011921:Rats, Inbred WKY; D013599:Systole
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002216:Captopril