Age-dependent changes in cardiac muscarinic receptor function in healthy volunteers

Institut fur Pharmakologie und Toxikologie, Universitat Halle-Wittenberg, Germany.

OBJECTIVES: This study was conducted to determine possible age-dependent changes in the responsiveness of human cardiac muscarinic receptors. BACKGROUND: It is well known that the baroreflex activity decreases with aging. However, the mechanisms underlying this phenomenon are not completely understood at present. METHODS: In six healthy young (mean [+/-SEM] age 26 +/- 2 years) and six healthy older volunteers (mean age 60 +/- 2 years), we determined 1) the effects of graded doses of atropine (bolus application, six doses, each for 20 min, range 0.03 to 0.96 mg) and the M1-cholinoceptor selective antagonist pirenzepine (bolus application, eight doses, each for 20 min, range 0.04 to 10 mg) on heart rate, blood pressure and systolic time intervals (as measure of inotropism); and 2) the baroreflex activity by assessing the bradycardic response to phenylephrine. RESULTS: Atropine and pirenzepine caused biphasic effects on heart rate: At lower doses (< 0.12 mg for atropine, < 5 mg for pirenzepine) they decreased heart rate, whereas at higher doses they increased heart rate. Heart rate decreases induced by both antimuscarinic drugs were significantly larger in the young volunteers than in the older volunteers, whereas heart rate increases were not significantly different for both drugs. Atropine and pirenzepine did not significantly affect blood pressure and systolic time intervals. Infusion of graded doses of phenylephrine (four doses ranging from 0.1 to 1.0 microgram/kg body weight per min for 15 min each) caused a higher increase in systolic blood pressure and a smaller decrease in heart rate at each dose in the older volunteers than in the young volunteers. The slopes of the regression lines were 16 +/- 2.3 ms/mm Hg for the young and 6 +/- 0.5 ms/mm Hg for the older volunteers (p < 0.01). CONCLUSIONS: Human cardiac muscarinic receptor activity is diminished with increasing age; such decreased cardiac muscarinic receptor activity could contribute to the decrease in baroreflex activity with aging. In contrast, antimuscarinic drugs seem to have no effect on human cardiac contractility.

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