VASCULAR ACTIONS OF OCTREOTIDE IN THE PORTAL HYPERTENSIVE RAT

1 We have investigated the actions of the somatostatin analogue octreo tide in the portal hypertensive Wistar rat in vivo and in rat small me senteric artery and aorta in vitro. 2 In small mesenteric artery, octr eotide (0.1-0.3 mu M) failed to produce any direct contraction, nor di d it affect contractions to noradrenaline (NA, 10 mu M) or endothelium -dependent relaxations to acetylcholine. 3 In rat aortal octreotide (0 .3 mu M) and somatostatin (1 mu M) failed to affect contractions to NA (1 mu M), or concentration-contractile response curves to NA. 4 In ra t vas deferens, octreotide and somatostatin significantly reduced cont ractile responses to electrical stimulation with pD(2) values (-log IC 50) of 8.19+/-0.10 (n=4) and 8.16+/-0.26 (n=4), respectively. Hence, t he lack of effect of these agents in aorta or mesenteric artery was no t due to lack of efficacy or inappropriate choice of concentration. 5 In the anaesthetized portal hypertensive rat, intravenous injection of octreotide (1-100 mu g kg(-1)) did significantly affect systemic bloo d pressure, nor did it affect mesenteric vascular conductance as measu red by laser doppler flow probes. However, octreotide (100 mu g kg(-1) ) significantly reduced vascular conductance to 74.2+/-7.7% of control (n=6) in porto-systemic shunt vessels as measured by laser doppler fl ow probes. 6 Phenylephrine (1 mu g kg(-1)) significantly raised blood pressure and significantly decreased vascular conductance in both mese nteric (66.6+/-3.7% of control) and porto-systemic shunt vessels (58.7 +/-10.0% of control). 7 It was concluded that octreotide has selective effects on porto-systemic shunt vessles in vivo in the portal hyperte nsive rat.