Altered responsiveness of adenylate cyclase to adenosine and other agents in the myocardial sarcolemma and aorta of spontaneously-hypertensive rats.
Adenylate cyclase activity was studied in the myocardial sarcolemma and aorta of spontaneously-hypertensive rats (SHR) and their respectively Wistar-Kyoto (WKY) controls. Basal enzyme activity was decreased in the SHR as compared to the WKY group. Adenylate cyclase stimulation by N-ethylcarboxamide adenosine (NECA) was significantly lower in the myocardial sarcolemma and aorta of SHR, and this decreased responsiveness was associated with a reduction in the Vmax. Other agonists, such as isoproterenol (ISO), epinephrine, dopamine (DA), and glucagon, also enhanced myocardial adenylate cyclase activity to various degrees in SHR and WKY, but stimulation (Vagonists/Vbasal) was always lower in the SHR. NaF and forskolin (FSK), which activate adenylate cyclase via receptor-independent mechanisms, augmented it in the myocardial sarcolemma of SHR to a lesser extent than in WKY. While the guanine nucleotides GTP and GMP-P(NH)P elevated adenylate cyclase in a concentration-dependent manner in both SHR and WKY, the magnitude of stimulation was significantly lower in the former group. Decreased basal adenylate cyclase activity and responsiveness to adenosine, various hormones, NaF and FSK were observed in SHR of all ages, i.e. from 4 to 24 weeks of age. In addition, basal, hormone-, NaF- and FSK-stimulated adenylate cyclase activity was diminished markedly in the aorta of SHR. These results suggest that, in SHR, not only is basal adenylate cyclase activity decreased but the abilities of adenosine, other hormones and agonists, such as NaF and FSK, to stimulate adenylate cyclase, guanine nucleotide regulatory protein and the catalytic subunit of the cyclase system are also impaired in the myocardial sarcolemma and aorta.
Anand-Srivastava
M B
MB
Clinical Research Institute of Montreal, Quebec, Canada.
D000241:Adenosine / Q000494:pharmacology*; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology*; D005576:Colforsin / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D005934:Glucagon / Q000494:pharmacology; D006973:Hypertension / Q000201:enzymology*; D066298:In Vitro Techniques; D009206:Myocardium / Q000648:ultrastructure*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012508:Sarcolemma / Q000187:drug effects / Q000201:enzymology
D005576:Colforsin; D005934:Glucagon; D000262:Adenylyl Cyclases; D000241:Adenosine; D004837:Epinephrine