Search

This study was designed to clarify the state of beta-adrenergic signal transduction and the disordered level of its transduction in hypertensive hearts, using myocardium from spontaneously hypertensive rats (SHR) as a generic model of essential hypertension. Beta-adrenergic receptor binding sites and dissociation constants in the extracted membranes of adult (70-100 days of age) SHR heart were not significantly different from those of Wistar-Kyoto (WKY) rats, the non-hypertensive control. The adenylate cyclase activities stimulated by isoproterenol with GTP, NaF and forskolin were significantly higher in SHR compared to those in WKY. To determine whether differences in signal transduction are natural or are a result of hypertension, we evaluated chronotropic responses in cultured cells of fetal hearts which had not been exposed to hypertension. Fetal cardiac muscle cells of SHR were more sensitive than WKY to isoproterenol stimulation over a wide concentration range. However, there were no statistically significant differences between these two strains with respect to the density of binding sites. These results suggest that in the transduction of adrenergic signals, alterations distal to the beta-receptors are present in the adult hearts of hypertensive rats, and, that the adrenergic signal transduction is already exaggerated in the pre-hypertensive fetal stage.

The effects of carvedilol (an alpha.beta-blocker) on lipid metabolism were assessed in addition to its hypotensive effect. The subjects were 18 men and 18 women, 20 with hypertension and 16 normotensives with other conditions requiring carvedilol treatment. They were aged from 31 to 79 years and were given a daily dose of 5-20 mg carvedilol (average, 9.7 mg/day) for 12 weeks. Significant falls were seen in blood pressure and heart rate after 12 weeks in the hypertensive subjects (mean +/- SE) (systolic: from 164 +/- 2 to 141 +/- 2 mm Hg, P less than 0.001; diastolic: from 98 +/- 1 to 85 +/- 2 mm Hg, P less than 0.001; heart rate: from 71 to 65 beats/min, P less than 0.001). Smaller changes in blood pressure and heart rate were seen in the normotensive subjects, with the fall in systolic pressure being significant (from 143 +/- 3 to 135 +/- 2 mm Hg, P less than 0.01). There were no significant changes in the overall serum total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and phospholipid levels. In the subgroup with a pretreatment serum triglyceride level of greater than 150 mg/dl, a significant fall of 52.1 mg/dl was seen (P less than 0.05). Lipoprotein analysis showed a significant fall in alpha-lipoprotein levels (P less than 0.05). The atherogenic index did not change significantly, and it was concluded that carvedilol was an effective antihypertensive agent that produced no adverse effects and possibly had beneficial effects on lipid metabolism.