The Role of Nitric Oxide in the Coronary Vasoconstriction Caused by Growth Hormone in Anaesthetized Pigs

Abstract

Intravenous injection of growth hormone in anaesthetized pigs has been shown to cause coronary vasoconstriction by antagonizing the vasodilatory effects of β2‐adrenergic receptors. Because nitric oxide is believed to modulate or mediate β2‐adrenergic effects, the present study was undertaken in the same experimental model to determine the role of nitric oxide in the above response to growth hormone. In fourteen pigs anaesthetized with sodium pentobarbitone, changes in left circumflex or anterior descending coronary blood flow caused by intravenous injection of 0.05 i.u. kg‐1 of growth hormone at constant heart rate and arterial blood pressure were assessed using electromagnetic flowmeters. In a first control group of six pigs, growth hormone caused a decrease in coronary blood flow which averaged 13.1% of the baseline values. In a second group of eight pigs, intravenous administration of Nω‐nitro‐L‐arginine methyl ester (L‐NAME) was used to block the endothelial release of nitric oxide. In these pigs, the subsequent injection of growth hormone did not cause any significant changes in coronary blood flow, even when performed after reversing the increase in arterial blood pressure and coronary vascular resistance caused by L‐NAME with continuous intravenous infusion of papaverine. These results indicated that the coronary vasoconstricting effect of growth hormone, known to involve antagonism of β2‐adrenergic vasodilatory effect, was mediated by inhibition of nitric oxide release.

The role of nitric oxide in the peripheral vasoconstriction caused by human placental lactogen in anaesthetized pigs

“…shown to be present mainly in the endothelium of the coronary vessels (Ursell & Mayes, 1993), and coronary microvessels have been demonstrated to be dilated both by β-adrenergic activation and by stimulation of nitric oxide release (Quillen et al 1992). Moreover, in the same experimental model as the present study, the release of nitric oxide has been shown to be involved in the coronary vasoconstriction caused by growth hormone (Molinari et al 2000) and in the coronary, mesenteric, renal and iliac vasoconstriction caused by dehydroepiandrosterone (Molinari et al 2003(Molinari et al , 2004, vascular effects which were demonstrated to be elicited by blockade of a tonic vasodilatory effect attributable to β 2 -adrenergic receptors.…”

Peptide Hormone Regulation of Angiogenesis

“…Loss of GH production in humans leads to increased peripheral resistance, reduced cardiac output, decreased blood flow in response to vasodilators, and reduced systemic NO levels, whereas GH replacement restores these responses to normal (58, 73, 391). Interestingly, some vasoconstrictive effects of GH via NO inhibition have also been reported in experimental settings (370).…”

The prolactin family hormones regulate vascular tone through NO and prostacyclin production in isolated rat aortic rings

“…Although the effects induced by PL on the vasculature are not fully understood, our data are among the first to suggest the role played by this hormone in the endothelium and in the NO-dependent relaxation of the aorta, a process that may be related to the redistribution of blood flow that occurs during pregnancy [7,54] . It is important to note that the experimental approaches utilized, as well as the conditions under which the experiments were undertaken, are important factors to consider, because the vasoconstrictor effects induced by GH and PL via the inhibition of NO have been reported in other vascular beds and in the setting of other experimental approaches [15,16,18] , findings suggestive of the differential actions of these hormones in different vascular beds. One possible explanation for these differential effects is the presence of the GHR in the endothelium.…”

“…The evidence indicates that PRL, GH, and PL induce regional vasoconstriction via the inhibition of NO-mediated vasodilation, a process regulated by the β2-adrenergic receptors in coronary, renal and iliac vessels in anesthetized pigs [15][16][17] . Supporting these findings, another study has demonstrated that transgenic mice overexpressing the bovine GH gene exhibited increased mean arterial blood pressure, an effect associated with decreases in the lumens of the vascular beds of the hindquarters, which resulted in the development of hypertension [18] .…”