41 Clinical Science (1999) 96, 41–47 (Printed in Great Britain) Portal hypertension increases vasoconstrictor responsiveness of rat aorta Claire CONNOLLY, Teresa CAWLEY, P. Aiden MCCORMICK* and James R. DOCHERTY Department of Physiology, Royal College of Surgeons in Ireland, Dublin 2, Ireland, and *Liver Unit, St. Vincent’s Hospital, Dublin 4, Ireland A B S T R A C T We have examined the effects of pre-hepatic portal hypertension on the responsiveness of aorta from Wistar and Sprague–Dawley rats. Rats were made portal hypertensive by creating a calibrated portal vein stenosis, or sham operated. In rat aorta, there was no significant difference between portal hypertensive and sham-operated animals in the contractile potency of KCl, noradrenaline or phenylephrine. In aortas from Wistar rats, the maximum response to KCl (0.71‡0.12 g) and noradrenaline (1.00‡0.17 g) but not phenylephrine (0.86‡0.10 g) in portal hypertensive animals was significantly increased compared with that in sham-operated animals (0.45‡0.04 g, 0.57‡0.07 g, 0.71‡0.05 g respectively). In aortas from Sprague–Dawley rats, the maximum response to KCl (1.21‡0.21 g) and phenylephrine (1.54‡0.30 g) but not nora- drenaline (0.93‡0.09 g) in portal hypertensive animals was significantly increased compared with that in sham-operated animals (0.59‡0.09 g, 0.76‡0.11 g, 1.04‡0.10 g respectively). There was no difference between portal hypertensive and sham-operated Wistar rats in the affinity or maximum number of binding sites for [ 3 H]prazosin to α 1 -adrenoceptors in cardiac ventricular membranes. It is concluded that portal hypertension tends to produce an increase rather than a decrease in the contractile response to vasoconstrictors in aorta from both Wistar and Sprague–Dawley rats. This suggests that the diminished responsiveness to vasoconstrictors reported in portal hypertensive rats in vivo is not due to a diminished responsiveness at the level of the vascular smooth muscle. INTRODUCTION The pre-hepatic portal hypertensive rat is a widely used model of human portal hypertension characterized by the development of portal-systemic shunting [1–3]. These shunts develop in response to the increased portal pressure, but a hyperdynamic circulatory state follows, characterized by increased cardiac output and increased splanchnic blood flow. The increased cardiac output and splanchnic blood flow may be due to the increased entry of gastrointestinal vasodilator hormones into the systemic circulation or to diminished responsiveness of Key words : acetylcholine, aorta, noradrenaline, phenylephrine, portal hypertension, Sprague–Dawley rat, Wistar rat. Correspondence : Professor J. R. Docherty. the systemic vasculature to endogenous vasoconstrictors. A number of vasodilator substances including glucagon and vascular endothelium-derived substances have been implicated [4,5]. It is generally assumed that responsiveness to vaso- constrictors is diminished in portal hypertension [3,6]. Many authors have reported decreased vascular respon- siveness to vasoconstrictors such as noradrenaline or angiotensin II in the mesenteric vascular beds of portal vein-ligated or cirrhotic rats in situ [7–10]. However, the presence of circulating vasodilators in these in situ studies may have influenced the actions of vasoconstrictors. # 1999 The Biochemical Society and the Medical Research Society