Relaxation of the aorta during hypoxia is impaired in chronically hypertensive rats.
We investigated mechanisms by which hypoxia produces relaxation of the aorta and tested the hypothesis that these mechanisms are altered during chronic hypertension. Tension of thoracic aortae from normotensive Wistar-Kyoto (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP) was measured in an organ bath under control conditions and at two levels of hypoxia. In WKY rats, mild and severe hypoxia produced relaxation of the aortae (precontracted with phenylephrine) by 33 +/- 4% and 82 +/- 3%, respectively (mean +/- SEM). Removal of endothelium or administration of NG-nitro-L-arginine (10(-4) mol/L), an inhibitor of nitric oxide synthase, abolished relaxation of the aortae in response to mild hypoxia but did not affect relaxation during severe hypoxia. Glibenclamide (10(-6) mol/L), an inhibitor of potassium channels, attenuated relaxation of the aortae during mild and severe hypoxia by 49 +/- 16% and 74 +/- 4%, respectively. In SHRSP, mild hypoxia produced little relaxation of the aortae (3 +/- 4%, P < .05 compared with WKY). Indomethacin did not increase relaxation to mild hypoxia in SHRSP, which suggests that a cyclooxygenase-derived contracting factor does not contribute to impaired relaxation. Severe hypoxia relaxed the aortae by 86 +/- 4% in SHRSP, and glibenclamide inhibited this response by 60 +/- 9%. These findings suggest that relaxation of the aorta in response to mild hypoxia in WKY rats is mediated primarily by endothelium-derived relaxing factor, and the response to mild hypoxia is markedly impaired in SHRSP.(ABSTRACT TRUNCATED AT 250 WORDS)
Taguchi
H
H
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
Faraci
F M
FM
Kitazono
T
T
Heistad
D D
DD
D000818:Animals; D001011:Aorta / Q000503:physiopathology*; D018999:Charybdotoxin; D002908:Chronic Disease; D005905:Glyburide / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D026902:Potassium Channel Blockers; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012604:Scorpion Venoms / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D026902:Potassium Channel Blockers; D012604:Scorpion Venoms; D018999:Charybdotoxin; D009599:Nitroprusside; D005905:Glyburide