Comparison of VIP and beta 2-adrenoceptor-induced relaxations in the circular and longitudinal smooth muscle layers of the rat portal vein.

The relative importance of VIP in reduction of vascular tone was studied in circular and longitudinal preparations of the VIP-innervated rat portal vein. Exogenous VIP inhibited the methoxamine-evoked contractures in the atropine-blocked preparations with a lower potency in the inner, circular (pD2 = 6.4 +/- 0.5, n = 6) than in the outer, longitudinal layer (pD2 = 7.7 +/- 0.1, n = 6). VIP was also a less efficient relaxant (intrinsic activity (alpha) = 0.60 +/- 0.16, n = 6) of the inner than of the outer layer (alpha = 1.00). The selective (salbutamol) and the non-selective (isoproterenol) beta 2-agonists completely relaxed the methoxamine contractures in both layers and the potency (isoproterenol) was higher in the inner (pD2 = 6.39 +/- 0.32, n = 6) than in the outer layer (pD2 = 5.67 +/- 0.34, n = 6). Plasma from the portal-mesenteric vein of anaesthetized, fasting rats contained 0.036 nM VIP (median, n = 17), that is, several orders of magnitude lower than the range of VIP concentrations relaxing the methoxamine contracted vein preparations via VIP receptors of the apamin-blockable category. The results support the hypothesis that alpha 1-adrenoceptor-induced contractions in the circular layer are predominately relaxed via beta 2-adrenoceptors while relaxation of the outer layer may occur via VIP receptors, probably activated by local release of the neuropeptide.

Comparison of atriopeptins II and III, VIP and beta 2-adrenoceptor-evoked relaxations of the two layers of smooth muscle in the rat portal vein.

The relative importance of vascular relaxations induced by atriopeptins (AP), the beta-adrenoceptor agonist isoprenaline and of the neuropeptide VIP was studied in vitro on circular and longitudinal preparations of the rat portal vein. Two members of the rat atriopeptins (AP II and III) were equipotent with respect to relaxation of the spontaneously contracting outer, longitudinal layer and of the alpha 1-contracted inner, circular layer. The potency for AP II was about 13 times lower in the inner (pD2 = 7.48 +/- 0.73, n = 6) than in the outer layer (pD2 = 8.60 +/- 0.34, n = 6). No significant difference was apparent between the intrinsic activities for AP II in the two layers. The potencies for AP II were for both layers higher than those for VIP while the intrinsic activities for AP II were significantly lower than for VIP and for the reference agonist, isoprenaline in both layers. Atriopeptin II was equally efficient in relaxing the K+-depolarized and alpha 1-contracted longitudinal segments. Neither the beta-antagonist, propranolol nor the guanylate cyclase inhibitor, methylene blue, modified the potency or the intrinsic activity of AP II. These results suggest that concentrations of circulating atriopeptins above 10 nM may contribute to reduction of vascular tone by the methylene blue insensitive receptors for AP II and III in the portal-mesenteric vein region.