Endothelium‐dependent and endothelium‐independent vasodilatation of the hepatic artery of the rabbit

Abstract

1 The isolated hepatic artery of the rabbit contracted to exogenously applied noradrenaline (NA). There was no significant difference in the maximal contraction or the EC50 value in vessels where the endothelium was present and in endothelium-denuded preparations. 2 Acetylcholine (ACh) induced a vasodilatation of vessels preconstricted with NA which was entirely dependent on the endothelium.3 Adenosine 5'-triphosphate (ATP), 2-methylthio ATP, adenosine and sodium nitroprusside induced concentration-dependent, sustained relaxations of vessels in which tone had been induced with NA. The relaxation responses were not reduced after removal of the endothelium. 8-Phenyltheophylline antagonized the relaxation response produced by adenosine, but not that due to ATP at lower concentrations. The maximum response to ATP was reduced in the presence of 8-phenyltheophylline. 4 a,,B-Methylene ATP produced further contraction of vessels preconstricted with NA in both endothelium-denuded preparations and in vessels where the endothelium remained intact. 5 Immunohistochemical analysis was used to show the presence of nerve fibres containing substance P (SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) in the hepatic artery. Application of SP induced a concentration-dependent relaxation which was entirely dependent on the presence of an intact endothelium. CGRP and VIP, however, elicited concentration-dependent relaxations which were independent of the endothelium. 7 It is concluded that in the rabbit hepatic artery, responses to ACh are dependent on the presence of intact endothelium. P1-, P2X-and P2,-purinoceptors, mediating relaxation to adenosine, vasoconstriction to ATP and vasodilatation to ATP respectively, are located on vascular smooth muscle. Furthermore, CGRP and VIP mediate a direct vasodilatation of smooth muscle both in the absence and the presence of the endothelium, whereas SP produces a relaxation via receptors located on the endothelium.

Nitric oxide‐related vasodilator responses to parasympathetic stimulation of the submandibular gland in the cat.

“…Endothelium-dependent responses have been reported to occur in rabbit mesenteric artery, isolated human arteries and veins and bovine intrapulmonary arteries (Itoh, Sasaguri, Makita, Kanmura & Kuriyama, 1985;Thom, Hughes, Martin & Sever, 1987;Ignarro, Byrns, Buga & Wood, 1987), while endothelium-independent responses have been encountered in cat cerebral arteries (Duckles & Said, 1982;Lee, Saito & Berezin, 1984), canine carotid arteries (D'Orleans-Juste, Dion, Mizrahi & Regoli. 1985), rabbit hepatic artery (Brizzolara & Burnstock, 1991), pig splenic and human skeletal muscle arteries (Pernow, 1989), bovine coronary arteries (Itoh, Lederis & Rorstad, 1990) and pulmonary arteries from man (Greenberg, Rhoden & Barnes, 1985) and rat, rabbit and guinea-pig (Hand, Laravuso & Will, 1984;Sata, Misra, Kubota & Said, 1986). Even more puzzling is the fact that the response to VIP of rat aorta has been reported to be both endothelium dependent (Davies & Williams, 1984;Sata, Linden, Liu, Kubota & Said, 1988) and endothelium independent (Schoeffter & Stoclet, 1985).…”

Purinergic Signaling and Blood Vessels in Health and Disease

“…Portally infused ATP leads to transhepatic vasodilatation via P2Y receptors on the endothelium, whereas ATP released from sympathetic nerves leads to vasoconstriction of hepatic arteries via P2X receptors on the muscle Burnstock, 1990, 1991;Phillips et al, 1998). Both endotheliumdependent and endothelium-independent vasodilation of rabbit hepatic artery mediated by purines has been described (Brizzolara and Burnstock, 1991). In the rabbit perfused liver, both P2X vasoconstrictor and P2Y vasodilator receptors (leading to release of NO) were identified (Mathie et al, 1991b;.…”

Nitric oxide is the mediator of ATP‐induced dilatation of the rabbit hepatic arterial vascular bed

“…Our conclusion was based on the observation that methylene blue attenuated relaxant responses to ATP and to the endothelium-dependent vasodilator acetylcholine (ACh), but not those to the endothelium-independent dilator, sodium nitroprusside (SNP), consistent with a direct inactivation of EDRF by methylene blue (Martin et al, 1985;Watanabe et al, 1988). However, the action of methylene blue may, at least partly, proceed through inhibition of smooth muscle guanylate cyclase (Martin et al;, thus leaving open the possibility that some of the relaxation to ATP could have taken place through direct action on a sub-population of P2y-purinoceptors located on the smooth muscle; this, in fact, has recently been shown to be the predominant location of these receptors in the common hepatic artery of the rabbit (Brizzolara & Burnstock, 1991).…”