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, and on contractile force in left ventricular strips of the rat heart. For comparison, eects of prostanoids on InsP-formation and contractile force were determined in rat thoracic aorta, a classical TP-receptor containing tissue. 2 Prostanoid increased InsP-formation and rate of protein synthesis in neonatal as well as adult rat cardiomyocytes; the order of potency was in neonatal (PGF 2a 4PGD 2 5PGE 2 5U 466194PGE 1 ) and adult (PGF 2a 4PGD 2 5PGE 2 4U 46619) rat cardiomyocytes well comparable. Moreover, in electrically driven left ventricular strips PGF 2a caused positive inotropic eects (pD 2 7.5) whereas U 46619 (up to 1 mM) was uneective. 3 In contrast, in rat thoracic aorta U 46619 was about 100 times more potent than PGF 2a in increasing InsP-formation and contractile force. 4 The TP-receptor antagonist SQ 29548 only weakly antagonized prostanoid-induced increases in rate of protein synthesis (pK B about 6) in rat cardiomyocytes but was very potent (pK B about 8 ± 9) in antagonizing prostanoid-induced increases in InsP-formation and contractile force in rat aorta. 5 We conclude that, in cardiomyocytes of neonatal and adult rats, the prostanoid-receptor mediating increases in InsP-formation and rate of protein synthesis is a FP-receptor. Moreover, stimulation of these cardiac FP-receptors can mediate increases in contractile force.

With increasing age, human myocardial uptake1 activity decreases, possibly because of age-dependent downregulation of uptake1 density.

Although saphenous veins and internal mammary arteries are commonly used for coronary artery bypass grafting, only a very few comparative studies are available on alpha-adrenoceptor-mediated vasoconstriction in these vessels. Thus, we determined, in isolated rings from human saphenous vein and human internal mammary artery, contractile responses to noradrenaline (10(-8)-10(-4) M) in the absence and presence of the alpha-adrenoceptor antagonists yohimbine (alpha(2)-adrenoceptor antagonist, 10(-8)-10(-6) M), prazosin (alpha(1)-adrenoceptor antagonist, 10(-9)-10(-7) M), 5-methyl-urapidil (5-MU, alpha(1A)-adrenoceptor antagonist, 10(-8)-10(-6) M), BMY 7378 (alpha(1D)-adrenoceptor antagonist, 10(-7)-10(-6) M), and chloroethylclonidine (CEC, irreversible alpha(1B)-adrenoceptor antagonist, 3x10(-5) M for 30 min). All experiments were carried out in the presence of 10(-7) M propranolol and 10(-5) M cocaine. In both vessel types noradrenaline evoked concentration-dependent contractions. In saphenous veins yohimbine was a potent antagonist (pA(2)-value 8.32) while prazosin, 5-MU and BMY exhibited only marginal antagonistic effects. CEC, however, significantly decreased noradrenaline-induced contractions. In contrast, in internal mammary arteries prazosin (pA(2)-value 9.65) and 5-MU (pK(B)-values 7.2-7.5) were potent antagonists, while yohimbine and BMY exhibited only weak antagonistic effects. CEC, however, significantly decreased noradrenaline-induced contractions. We conclude that in saphenous vein the contractile response to noradrenaline is mediated predominantly by alpha(2)-adrenoceptors, while in internal mammary artery it is mediated (to a major part) by alpha(1B)- and (to a minor part) by alpha(1A)-adrenoceptors.

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