Reduced function of the stimulatory GTP-binding protein in beta adrenoceptor-adenylate cyclase system of femoral arteries isolated from spontaneously hypertensive rats.
Arterial relaxant responses to beta adrenoceptor agonists are decreased in spontaneously hypertensive rats (SHR) when compared with normotensive Wistar-Kyoto rats (WKY). To determine which component of the beta adrenoceptor-adenylate cyclase (AC) system is involved in the decreased beta adrenoceptor responses, effects of two activators of AC-forskolin and cholera toxin and of dibutyryl cyclic AMP (DBcAMP) were compared between the strips of femoral arteries isolated from 13-week-old SHR and age-matched WKY. Arterial relaxant responses to either forskolin, an activator of AC or DBcAMP were not significantly different between the SHR and WKY, whereas the relaxant responses to norepinephrine (NE) via beta adrenoceptors were significantly weaker in the SHR than in the WKY. In the absence of timolol, a beta adrenoceptor antagonist, contractile responses to NE were significantly greater in the SHR than in the WKY. Timolol augmented the contractile responses to NE to a greater extent in the WKY than in the SHR. After the blockade by timolol of beta adrenoceptors, contractile responses to alpha adrenoceptor stimulation with NE were not significantly different between the two strains. The pretreatment of the strips with cholera toxin, an activator of stimulatory GTP-binding protein (Gs), antagonized the alpha adrenoceptor-mediated contractions much greater in the WKY than in the SHR. The alpha adrenoceptor-mediated contractions after the pretreatment with cholera toxin were comparable to the contractile responses to NE determined in the absence of timolol in either the SHR or the WKY. Forskolin and DBcAMP also antagonized the alpha adrenoceptor-mediated contractions. However, these antagonisms were not significantly different between the two strains. The cellular cAMP content in arterial strips after the stimulation with NE was significantly less in the SHR than in the WKY, whereas the cAMP contents were similar in arterial strips from both strains which were stimulated with forskolin. These results suggest that the reduced function of Gs is involved in the abnormality of beta adrenoceptor-AC system in the SHR femoral artery.
Asano
M
M
Department of Pharmacology, Nagoya City University Medical School, Japan.
Masuzawa
K
K
Matsuda
T
T
Asano
T
T
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis; D005263:Femoral Artery / Q000187:drug effects / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D013045:Species Specificity; D014661:Vasoconstriction / Q000187:drug effects
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D009599:Nitroprusside; D005576:Colforsin; D003994:Bucladesine; D002772:Cholera Toxin; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D015056:1-Methyl-3-isobutylxanthine