Abstract
BIOCHEMICAL modifications in cardiac hyptertrophy, secondary to high blood pressure, in spontaneously hypertensive (SH) rats, include reduced receptor reactivities to isoproterenol1,2 and glucagon3, and lower contents of cyclic AMP and cyclic GMP due to aberrations in adenylate and guanylate cyclases or phosphodiesterases, or both. Also possibly affected are cyclic AMP-dependent protein kinase (A-PK) and cyclic GMP-dependent protein kinase (G-PK), enzymes that presumably mediate the effects of the respective cyclic nucleotide in vivo. An accurate assay for G-PK from mammalian tissues is possible in the presence of stimulatory modulator (specifically stimulating G-PK), either as a separated and purified form4 or as a mixture with inhibitory modulator (specifically inhibiting A-PK) in a form of crude protein kinase modulator5,6. We have examined possible involvements of cardiac G-PK, relative to A-PK, in chronic hypertension and possible effects of guanethidine, a hypotensive drug, on the two key enzymes. We found that the cardiac level of G-PK in spontaneously hypertensive rats was lower than that in normotensive rats, whereas that of A-PK was the same in both groups. Guanethidine depressed the former enzyme further without affecting the latter.
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KUO, J., DAVIS, C. & TSE, J. Depressed cardiac cyclic GMP-dependent protein kinase in spontaneously hypertensive rats and its further depression by guanethidine. Nature 261, 335–336 (1976). https://doi.org/10.1038/261335a0
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DOI: https://doi.org/10.1038/261335a0
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