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From the Second Department of Internal Medicine, Faculty of Medicine,
Kyushu University, Fukuoka, Japan.
Correspondence to Uran Onaka, MD, Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Maidashi 3–1-1, Higashi-ku, Fukuoka, 812–8582, Japan. E-mail fujii{at}intmed2.med.kyushu-u.ac.jp
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.
Methods and 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 · kg-1 · d-1) (SHR-Es) or a
combination of hydralazine (25 mg ·
kg-1 · d-1) and
hydrochlorothiazide (7.5 mg ·
kg-1 · 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
NG-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.
© 1998 American Heart Association, Inc.
Basic Science Reports
Antihypertensive Treatment Improves Endothelium-Dependent Hyperpolarization in the Mesenteric Artery of Spontaneously Hypertensive Rats
Key Words: endothelium-derived factors • arteries • hypertension • drugs
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