Exp Physiol 91.3 pp 603–610 603 Experimental Physiology The role of nitric oxide in the peripheral vasoconstriction caused by human placental lactogen in anaesthetized pigs C. Molinari, E. Grossini, D. A. S. G. Mary, F. Ribichini, N. Surico and G. Vacca Dipartimento di Scienze Mediche, Facolt` a di Medicina e Chirurgia, Universit` a del Piemonte Orientale ‘A. Avogadro’, via Solaroli 17, I-28100 Novara, Italy Regional intra-arterial infusion of human placental lactogen in anaesthetized pigs has been shown to cause coronary, renal and iliac vasoconstriction by antagonizing the vasodilatory effects of β 2 - adrenergic receptors. Since nitric oxide is known to modulate or mediate β 2 -adrenergic effects, the present study was planned in the same experimental model to determine the role of nitric oxide in the above vascular responses to human placental lactogen. In eight pigs anaesthetized with sodium pentobarbitone, changes in anterior descending coronary, left renal and left internal iliac blood flow caused by intra-arterial infusion of human placental lactogen at constant heart rate and arterial blood pressure were assessed using electromagnetic flowmeters. Intra-arterial infusion of the human placental lactogen caused decreases in coronary, renal and iliac blood flow which, respectively, averaged 16.7, 8.1 and 12.2% of the baseline values. The role of nitric oxide in this response was studied in the same pigs by repeating the experiments, after measured blood flows had returned to baseline values, following intra-arterial administration of N ω -nitro- L-arginine methyl ester (L-NAME). The subsequent intra-arterial infusion of human placental lactogen did not cause any significant changes in measured blood flows, even when performed after reversing the increase in arterial blood pressure and coronary, renal and iliac resistance caused by L-NAME with continuous intravenous infusion of papaverine. These results indicate that the coronary, renal and iliac vasoconstriction caused by human placental lactogen, known to involve antagonism of β 2 -adrenergic vasodilatory effects, was mediated by inhibition of nitric oxide release. (Received 11 November 2005; accepted after revision 27 February 2006; first published online 2 March 2006) Corresponding author C. Molinari: Facolt` a di Medicina e Chirurgia, via Solaroli 17, I-28100 Novara, Italy. Email: molinari@med.unipmn.it The hormone human placental lactogen is known to play an important role in lactation, reproduction, osmoregulation, immunomodulation and growth of tissues and blood vessels (Goffin et al. 1996; Kann et al. 1999; Karabulut et al. 2001; Corbacho et al. 2002). It has also been associated with pregnancy-induced hypertension, pre-eclampsia and umbilical vascular resistance (Obiekwe et al. 1984; Bewley et al. 1993; Murai et al. 1997). Recently, intra-arterial infusion of human placental lactogen in anaesthetized pigs was shown to cause coronary, renal and iliac vasoconstriction through blockade of tonic vasodilatory effects attributable to β 2 -adrenergic receptors (Grossini et al. 2006). A tonic β 2 -adrenergic receptor-mediated vasodilatation is known to occur in several peripheral vascular beds in anaesthetized pigs (e.g. Vacca et al. 1996). This effect has been reported to be modulated or mediated by the endothelial release of nitric oxide in the coronary and peripheral vasculature (Quillen et al. 1992; Parent et al. 1993; DiCarlo et al. 1995; Persson, 1996), although other reports have not confirmed this in isolated coronary arteries (Macdonald et al. 1987; Xu & Huang, 2000). This raised the possibility that endothelial nitric oxide may be involved in human placental lactogen-induced coronary, renal and iliac vasoconstriction, which has been attributed to inhibition of β 2 -adrenergic receptor- mediated vasodilatory effects. The present work in anaesthetized pigs was therefore designed to establish the role of nitric oxide in the coronary, renal and iliac vasoconstriction caused by human placental lactogen that is mediated through inhibition of the vasodilatory effects of β 2 -adrenergic receptors. This was C  2006 The Authors. Journal compilation C  2006 The Physiological Society DOI: 10.1113/expphysiol.2005.032755