Role of cyclic AMP protein kinase in decreased arterial cyclic AMP responsiveness in hypertension.
A decreased relaxation responsiveness to isoproterenol and forskolin is manifest in aortic smooth muscle isolated from spontaneously hypertensive rats (SHR) when compared with normotensive Wistar Kyoto (WKY) rats. Inasmuch as the effector of cyclic AMP (cAMP) is cAMP-dependent protein kinase, we sought to determine if alterations in this enzyme might be responsible for this decreased responsiveness to cAMP-increasing vasodilators. The concentration of cAMP protein kinase activity in aortic, carotid and caudal arteries (approximately 300 pmol/mg of protein per min) was similar in both WKY and SHR. Activity in femoral arteries from SHR and WKY rats was greater (approximately 600 pmol/mg/min); branches of the femoral artery from SHR had less protein kinase activity (660 pmol/mg/min) than their WKY counterparts (1000 pmol/mg/min). There were no differences between WKY and SHR in isozymic distribution of soluble cAMP protein kinase in any of these sources of arterial smooth muscle. Concentration and temporal-related relaxation of KCl-contracted aortic muscle strips by forskolin was associated with concomitant activation of cAMP protein kinase in both groups. The rate and extent of kinase activation was similar for both groups even though the rate and extent of relaxation was markedly less in SHR. These findings show that neither the concentration, isozymic distribution nor activation of cAMP-dependent protein kinase are different in aortic smooth muscle isolated from SHR when compared with WKY animals. Thus, decreased relaxation responsiveness to cAMP-increasing vasodilators is probably not related to events proximal to and including activation of arterial cAMP-dependent protein kinase.
Silver
P J
PJ
Michalak
R J
RJ
Kocmund
S M
SM
D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology; D001158:Arteries / Q000201:enzymology; D005576:Colforsin; D000242:Cyclic AMP / Q000378:metabolism* / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006973:Hypertension / Q000201:enzymology* / Q000503:physiopathology; D007527:Isoenzymes / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects
D004224:Diterpenes; D007527:Isoenzymes; D005576:Colforsin; D000242:Cyclic AMP; D011494:Protein Kinases; D007545:Isoproterenol