Effects of glucagon-like peptide-1(7-36) amide on neurohypophysial and cardiovascular functions under hypo- or normotensive hypovolaemia in the rat

Abstract

To date, glucagon-like peptide 1(7-36) amide (tGLP-1) has been found to affect the neurohypophysial and cardiovascular functions in normotensive and normovolaemic rats. The aim of the present study was to investigate possible effects of tGLP-1 on the mean arterial blood pressure and the release of vasopressin and oxytocin under conditions of blood volume depletion in the rat. In the first series of experiments, the animals were injected i.p. with either 0·15 M saline or 30% polyethylene glycol (PEG). PEG caused an 18% reduction of blood volume 1 h after injection. No significant changes in the mean arterial blood pressure were found in either normo-or hypovolaemic rats during the experiment. tGLP-1 injected i.c.v. at a dose of 1 µg/5 µl 1 h after the i.p. injection increased similarly the arterial blood pressure in normoand hypovolaemic rats. The plasma vasopressin/oxytocin concentrations were markedly elevated in hypovolaemic animals and tGLP-1 further augmented the release of both hormones. In the second study, hypovolaemia was induced by double blood withdrawal. The haemorrhage resulted in a marked decrease of the mean arterial blood pressure and in the elevated plasma vasopressin/oxytocin concentrations. tGLP-1 injected immediately after the second blood withdrawal increased the arterial blood pressure. In parallel, tGLP-1 enhanced significantly vasopressin and oxytocin secretion when compared with haemorrhaged, saline-injected rats. The results of this study indicate that tGLP-1 may affect the arterial blood pressure and the secretion of neurohypophysial hormones under pathological conditions brought about by blood volume depletion.

Mesenteric Vasoconstriction and Hindquarters Vasodilatation Accompany the Pressor Actions of Exendin-4 in Conscious Rats

“…However, the mesenteric vasoconstriction was clearly active (i.e., involved a substantial reduction in flow). Given the ability of GLP-1 receptor agonists to release vasopressin (Bojanowska and Stempniak, 2002) and given the potent effects of vasopressin to cause mesenteric vasoconstriction in conscious rats (Gardiner et al, 1988), we had anticipated that a V 1 receptor antagonist would suppress the mesenteric vasoconstrictor effects of exendin-4 in the presence of propranolol and phentolamine. However, this was not the case, despite some previous findings indicating an involvement of vasopressin in the pressor effects of GLP-1 receptor agonism (Isbil-Buyukcoskun and Gulec, 2004).…”

“…However, none of the published studies on GLP-1-(7-36) amide or exendin-4 have measured the underlying hemodynamic changes accompanying the pressor effects. In the light of the findings reported above, we hypothesized that the cardiovascular effects of exendin-4 are an amalgam of sympathoadrenal activation (with ␣-adrenoceptor-mediated vasoconstriction offsetting ␤-adrenoceptor-mediated vasodilatation), vagal withdrawal (Barragá n et al, 1999), vasopressin release (Bojanowska and Stempniak, 2002), and renin release (Malendowicz et al, 2003). To test our hypothesis, experiments were performed in conscious, chronically instrumented rats in which we monitored the regional hemodynamic responses to exendin-4 in the absence and presence of selected pharmacological antagonists.…”

Glucagon-Like Peptide-1 and Blood Pressure in Young and Healthy Adults from the General Population

“…Recent studies suggest BP-lowering effects of GLP-1RA. [20][21][22][23] In contrast, some [24][25][26] but not all 16 experimental studies showed a rise in BP after GLP-1 injection.…”

Mechanisms Involved in Glucagon-Like Peptide-1 (7–36) Amide Action on the Rat Hypothalamo-Neurohypophysial System

“…The vasopressin and oxytocin concentrations in the medium samples were measured by radioimmunoassay [3]. Anti-oxytocin and anti-vasopressin antibodies were raised by Dr. Monika Orlowska-Majdak (Department of Physiology, Medical University of Lodz).…”

“…Glucagon-like peptide-1 (7–36) amide (tGLP-1), a peptide of the gut-brain axis, has been found to increase the release of neurohypophysial hormones in vivo [1, 2, 3]and in vitro [4]. The latter effect, however, was only noted in the intact hypothalamo-neurohypophysial complex (HNC) [4]and not in isolated neurohypophyses [5].…”