Role of afferent nerves and sensory peptides in the mediation of hepatic artery buffer response.
Intrahepatic arteries are richly innervated by both adrenergic and sensory vanilloid-sensitive (capsaicin-sensitive) fibers. Stimulation of capsaicin sensitive fibers has been shown to dilate the intrahepatic vessels by both releasing sensory neuropeptides and by modulating the adrenergic tone. However the participation of capsaicin-sensitive fibers in the mediation of the hepatic artery buffer response (HABR) has not been investigated yet. To explore the involvement of sensory innervation and sensory neuropeptides in the HABR, the experiments were performed on capsaicin-denervated Wistar rats. In addition, we used selective CGRP and tachykinin receptor antagonists to test the participation of CGRP, substance P and NK-A in HABR in the rat. In anesthetized rats the hepatic artery blood flow (HABF), microcirculatory hepatic blood flow (HBF) and portal blood flow (PBF) were determined. The HABR was induced by partial occlusion of the portal vein and maintaining the PBF at 10% of its control preocclusive value. In the control HABR the hepatic artery blood flow increased by 89% (p< 0.005) whilst the HBF at the same time decreased by 32% (p< 0.005) in comparison to preocclusive HABF and HBF values. In sensory-denervated rats the resting HBF and PBF were increased by 23% (p< 0.05) and 34% (p< 0.05), respectively in comparison to the control HBF and PBF values. In this group the induction of the HABR increased the hepatic artery blood flow by only 55% (p< 0.05), whilst the HBF was reduced by 45% (p< 0.05). Pretreatment with CGRP 8-37 (CGRP receptor antagonist) and NK-1 but not NK-2 nor NK-3 receptor antagonists significantly reduced the HABF by 43% (p< 0.05) and 25% (p< 0.05) as compared to the HABF value in the control HABR group. These findings support the hypothesis that the hepatic artery buffer response induced by reduction of the portal inflow to the liver by 90% is partially mediated by activation of capsaicin-sensitive sensory fibers in the liver, probably due to local tissue ischemia and hypoxia. The observed vasodilation in the vascular bed of the hepatic artery is due to stimulation of CGRP and NK-1 receptors.
Biernat
J
J
Department of Physiology, Jagiellonian University, Medical College, Cracow, Poland. biernat2@poczta.onet.pl
Pawlik
W W
WW
Sendur
R
R
Dembiński
A
A
Brzozowski
T
T
Konturek
S J
SJ
D000818:Animals; D006499:Hepatic Artery / Q000502:physiology*; D008099:Liver / Q000098:blood supply / Q000502:physiology; D008833:Microcirculation / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018000:Receptors, Peptide / Q000502:physiology*
D018000:Receptors, Peptide