L-arginine restores dilator responses of the basilar artery to acetylcholine during chronic hypertension.
The objective of this study was to test the hypothesis that administration of L-arginine, a substrate for nitric oxide synthase, restores acetylcholine-induced dilatation of the basilar artery in chronically hypertensive rats. Basilar artery diameter was measured through a cranial window in anesthesized stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) aged 6 to 7 months (adult) and 12 months (older adult). Under control conditions, baseline basilar artery diameter was smaller in SHRSP (adult, 239 +/- 30 micron; older adult, 198 +/- 13 micron) (mean +/- SE) than in WKY (adult, 261 +/- 10 micron; older adult, 259 +/- 7 micron) (P <.05 versus SHRSP). Topical application of acetylcholine (10(-5) mol/L) produced dilatation of the basilar artery in WKY, which was impaired in both adult and older SHRSP (P <.05). Topical L-arginine (10(-3) mol/L for 30 minutes) did not affect responses to acetylcholine in adult SHRSP but enhanced vasodilatation in response to acetylcholine (10(-5) mol/L) in older SHRSP without affecting responses to sodium nitroprusside. In contrast, D-arginine did not affect acetylcholine-induced vasodilatation in older SHRSP. These results suggest that impaired dilatation of the basilar artery in response to acetylcholine in older SHRSP is restored toward normal by L-arginine, a substrate for nitric oxide synthase.
Kitazono
T
T
Department of Internal Medicine, Cardiovascular Center, University of Iowa College of Medicine, Iowa City 52242, USA.
Faraci
F M
FM
Heistad
D D
DD
D000109:Acetylcholine / Q000008:administration & dosage*; D000818:Animals; D001120:Arginine / Q000008:administration & dosage*; D001488:Basilar Artery / Q000502:physiology*; D002908:Chronic Disease; D004347:Drug Interactions; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014664:Vasodilation / Q000187:drug effects*
D001120:Arginine; D000109:Acetylcholine