ENHANCEMENT IN MYOCARDIAL INOTROPIC RESPONSE TO BAY K-8644 WITH ADVANCING AGE

In the present study, age-related alterations in cardiovascular response to Ca2+ agonist BAY K 8644 were investigated in rats. Dose response of BAY K 8644 (1-30-mu-g/kg) was studied in open chest rats by intravenous bolus administration. Maximum elevation of mean arterial pressure and (+)dp/dt of left ventricular pressure were significantly higher and the dose of BAY K 8644 required to produce half maximal response was substantially lower in 12 months old (4-mu-g/kg) than in 2 months old (10 gg/kg) rats. Larger doses of BAY K 8644 produced arrhythmias only in 12 months old rats, which was not totally abolished by nitroglycerine pretreatment. Perfusion of isolated rat hearts with 10(-6) M BAY K 8644 produced positive inotropic response, which was on the average 50% greater and developed much faster in 12 months old than in 2 months old rats. It is therefore concluded that the myocardial sensitivity to BAY K 8644 increases during adult maturation.