Attenuation of alpha-adrenergic responsiveness in hypoxic SHR.
Chronic exposure to hypoxia reduces the severity of hypertension in SHR. This study explored the possibility that hypoxic moderation of spontaneous hypertension is caused by a decrease in vascular responsiveness. In vitro studies were conducted with thoracic aortic rings obtained from SHR and Wistar-Kyoto (WKY) rats maintained under hypoxic (H; simulated altitude = 3658 m) and normoxic (N; laboratory altitude = 1520 m) conditions. Vessels were removed prior to the rapid development of hypertension (5 weeks of age; 3 days of altitude exposure), during the rapid hypertension-development stage (10 weeks of age; 5 weeks of altitude exposure), and during the established hypertension stage (18 to 20 weeks of age; 11 to 13 weeks of altitude exposure). Dose-response curves were obtained using a non-specific vasoconstrictor (KCl) and an alpha-adrenergic agonist, phenylephrine. At all ages, WKY vessels developed greater maximal contraction to vasoconstrictor stimuli, whereas vessels from the two older groups of SHR were more sensitive (more responsive at lower dosages) to KCl. Hypoxia caused significant (p less than 0.05) attenuation of the contractile responses to phenylephrine in young "pre-hypertensive" SHR, while similar, though less marked, attenuation of phenylephrine responsiveness was evident in young WKY-H. Chronically-reduced responsiveness to phenylephrine was found in vessels from SHR-H but not WKY-H. The lack of hypoxia-induced changes in vessel response to the non-specific vasoconstrictor, KCl, suggests a specific hypoxic attenuation of adrenergic vascular responsiveness. Thus, hypoxia may protect against the development of spontaneous hypertension through attenuation of alpha-adrenergic vasoconstrictor mechanisms.
D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D001794:Blood Pressure; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000150:complications / Q000151:congenital / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000187:drug effects*
D010656:Phenylephrine; D011189:Potassium Chloride