Experiments were conducted to determine if substrate-specific changes in microsomal metabolism and liver proteins occurred in young (12–13 weeks) spontaneously hypertensive rats (SHR) fed ad libitum compared to age-matched normotensive Wistar Kyoto (WKY) control rats. The hepatic microsomal protein content in SHR rats was significantly increased compared to WKY rats while cytosolic and total liver protein levels did not differ between the two groups. Liver microsomal ethylmorphine-N-demethylase activity was substantially enhanced in SHR rats with only slight increases in cytochrome P-450 content and aniline hydroxylase activity compared to WKY rats. The substrate-specific increases in the microsomal drug metabolism in SHR rats were accompanied by an increase in the prominence of a protein with molecular weight 55,000 in the cytochrome P-450 region. These preliminary observations may be clinically relevant in that alterations in hepatic drug metabolism may be associated with endogenous biochemical processes underlying the hypertensive state.

Daily variations in hepatic drug metabolism and in plasma corticosterone and insulin levels were examined at monthly intervals over the duration of 1 year. Annual differences were observed in the basal levels of all parameters. Consistent daily variations were observed only in plasma corticosterone levels, whereas daily variations in each of the other parameters occurred inconsistently over the year with significant variations being found in ethylmorphine metabolism and insulin levels only five times, and in aniline metabolism, six times. These data show that daily variations in the parameters examined do not occur in a regular manner.

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