| 10608476 |
Ge C, Garcia R, Anand-Srivastava MB: Altered expression of Gi-protein and adenylyl cyclase activity in hearts from one kidney one clip hypertensive rats: effect of captopril. J Hypertens. 1999 Nov;17(11):1617-26.
OBJECTIVE: To investigate whether one kidney one clip (1K-1C) hypertensive rats associated with high levels of angiotensin II (Ang II) exhibit enhanced expression and functions of G proteins in the heart and whether the enhanced expression can be attributed to Ang II. METHODS: The levels of G protein and G protein mRNA in hearts from 1K-1C hypertensive rats were determined by immunoblotting and Northern blotting techniques using specific antibodies and cDNA probes, respectively, for different isoforms of G proteins. Adenylyl cyclase activity, stimulated or inhibited by agonists, was determined to examine the function of G proteins. RESULTS: The levels of Gialpha-2 and Gialpha-3 proteins and mRNA were significantly increased in hearts from 1K-1C hypertensive rats compared with control rats, whereas the levels of Gsalpha were unchanged. Guanosine 5'-[3'-thio] triphosphate (GTPgammaS), isoproterenol, glucagon, sodium fluoride (NaF) and forskolin (FSK) stimulated adenylyl cyclase activity in hearts from control and hypertensive rats to varying degrees; however, the stimulations were significantly less in hypertensive rats compared with control rats. On the other hand, the inhibitory effect of low concentrations of GTPgammaS on FSK-stimulated adenylyl cyclase activity (an index of Gi function) was significantly enhanced in hearts from 1K-1C hypertensive rats, whereas the inhibitory effect of C-ANF4-23 on adenylyl cyclase was increased and that of Ang II was decreased in hearts from 1K-1C hypertensive rats. Captopril, an angiotensin-converting enzyme inhibitor, restored the augmented levels of Gi proteins and also the altered stimulation and inhibition of adenylyl cyclase by GTPgammaS, stimulatory and inhibitory hormones, respectively, in hearts from hypertensive rats. CONCLUSION: These data suggest that 1K-1C hypertensive rats exhibit enhanced expression of Gialpha proteins and associated functions that may be attributable to the enhanced levels of Ang II in this model of hypertension. |
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