The effect of dehydroepiandrosterone on coronary blood flow in prepubertal anaesthetized pigs

Extensive research suspecting an association between plasma levels of dehydroepiandrosterone and the risk of coronary heart disease has not been conclusive. The present study was designed to investigate the effect of dehydroepiandrosterone on the coronary circulation and to determine the mechanisms involved. In prepubertal pigs of both sexes anaesthetized with sodium pentobarbitone, changes in left circumflex or anterior descending coronary flow caused by intravenous infusion of dehydroepiandrosterone were assessed using an electromagnetic flowmeter. Changes in heart rate and arterial pressure were prevented by atrial pacing and by connecting the arterial system to a pressurized reservoir containing Ringer solution. In 20 pigs, infusion of 1 mg h−1 of dehydroepiandrosterone caused a decrease in coronary flow without affecting left ventricular dP/dtmax (rate of change of left ventricular systolic pressure) and filling pressures of the heart. In a further eight pigs, a dose–response curve was obtained by graded increases in the infused dose of hormone between 0.03 and 4 mg h−1. The mechanisms of the above response were studied in the 20 pigs by repeating the experiment after haemodynamic variables had returned to the control values observed before infusion. Blockade of muscarinic cholinoceptors with intravenous atropine (five pigs) and of α-adrenoceptors with intravenous phentolamine (five pigs) did not affect the dehydroepiandrosterone-induced coronary vasoconstriction. This response was abolished by blockade of β-adrenoceptors with intravenous propranolol (five pigs) and of coronary nitric oxide synthase with intracoronary injection of Nω-nitro-l-arginine methyl ester (five pigs) even after reversing the increase in arterial pressure and coronary vascular resistance caused by the two blocking agents with intravenous infusion of papaverine. The present study showed that intravenous infusion of dehydroepiandrosterone primarily caused coronary vasoconstriction. The mechanisms of this response were shown to involve the inhibition of a vasodilatory β-adrenergic receptor-mediated effect related to the release of nitric oxide

Effect of Dehydroepiandrosterone Replacement on Lipoprotein Profile in Hypoadrenal Women

Context: Levels of dehydroepiandrosterone (DHEA) and its sulfate form (DHEAS) are inversely associated with cardiovascular mortality in men but not women. Very little evidence is available on the impact of DHEA administration on lipoprotein profile in women. DHEAS levels are very low/undetectable in hypoadrenal women

The effect of dehydroepiandrosterone on regional blood flow in prepubertal anaesthetized pigs

Dehydroepiandrosterone has been implicated in vascular disease and its associated insulin resistance and hypertension, though little is known about its vascular effects. We have recently shown in prepubertal anaesthetized pigs that intravenous infusion of dehydroepiandrosterone caused coronary vasoconstriction through the inhibition of a vasodilatory β-adrenergic receptor-mediated effect related to the release of nitric oxide. The present study was designed to investigate the effect of dehydroepiandrosterone on mesenteric, renal and iliac vascular beds. In prepubertal pigs of both sexes anaesthetized with sodium pentobarbitone, changes in superior mesenteric, left renal and left external iliac blood flow caused by intravenous infusion of dehydroepiandrosterone were assessed using electromagnetic flowmeters. Changes in heart rate and arterial blood pressure were prevented by atrial pacing and by connecting the arterial system to a pressurized reservoir containing Ringer solution. In 22 pigs, infusion of 1 mg h(−1) of dehydroepiandrosterone decreased mesenteric, renal and iliac blood flow. In a further 10 pigs, dose–response curves were obtained by graded increases in the infused dose of hormone between 0.03 and 4 mg h(−1). The mechanisms of the above response were studied in the 22 pigs by repeating the experiment after haemodynamic variables had returned to the control values observed before infusion. Blockade of α-adrenoceptors with intravenous phentolamine (five pigs) did not affect the dehydroepiandrosterone-induced mesenteric, renal and iliac vasoconstriction. This response was abolished by blockade of β(2)-adrenoceptors with intravenous butoxamine (five pigs) and by blockade of mesenteric, renal and iliac nitric oxide synthase with intra-arterial administration of N(ω)-nitro-l-arginine methyl ester (seven pigs), even after reversing the increase in local vascular resistance caused by the two blocking agents with intravenous infusion of papaverine. In five pigs, the increase in measured blood flow caused by intravenous infusion of isoproterenol (isoprenaline) was significantly reduced by infusion of dehydroepiandrosterone. The present study showed that intravenous infusion of dehydroepiandrosterone primarily caused mesenteric, renal and iliac vasoconstriction. The mechanisms of this response were shown to be due to the inhibition of a vasodilatory β(2)-adrenergic receptor-mediated effect, which possibly involved the release of nitric oxide