Cirrhosis decreases vasoconstrictor response to electrical field stimulation in rat mesenteric artery: role of calcitonin gene‐related peptide

• Published in: Experimental physiology 2011-03, Vol.96 (3), p.275-286
• Main Authors: Blanco‐Rivero, Javier, Márquez‐Rodas, Iván, Sastre, Esther, Cogolludo, Ángel, Pérez‐Vizcaíno, Francisco, del Campo, Lara, Nava, Ma Paz, Balfagón, Gloria
• Format: Article
• Language: English
• Subjects: Animals; Arteries; ATP-Binding Cassette Transporters - biosynthesis; ATP-Binding Cassette Transporters - genetics; Calcitonin; Calcitonin gene-related peptide; Calcitonin Gene-Related Peptide - pharmacology; Calcitonin Receptor-Like Protein - blood; Calcitonin Receptor-Like Protein - genetics; Carbon Tetrachloride - pharmacology; Channel gating; Cirrhosis; Cyclic GMP; Cyclic GMP - analogs & derivatives; Cyclic GMP - metabolism; Cyclic GMP - pharmacology; Electric fields; Electric Stimulation - methods; glibenclamide; Glyburide - pharmacology; Guanylate cyclase; KATP Channels - drug effects; KATP Channels - metabolism; KATP Channels - physiology; Liver; Liver Cirrhosis - metabolism; Liver Cirrhosis - physiopathology; Male; Mesenteric Arteries - drug effects; Mesenteric Arteries - metabolism; Mesenteric Arteries - physiology; Muscle Cells - drug effects; Muscle Cells - metabolism; Myocytes; Oxadiazoles - pharmacology; Peptide Fragments - pharmacology; pinacidil; Pinacidil - pharmacology; Potassium Channels, Inwardly Rectifying - biosynthesis; Potassium Channels, Inwardly Rectifying - genetics; Quinoxalines - pharmacology; Rats; Rats, Sprague-Dawley; Receptor activity modifying proteins; Receptor Activity-Modifying Protein 1 - biosynthesis; Receptor Activity-Modifying Protein 1 - genetics; Receptors, Calcitonin Gene-Related Peptide - antagonists & inhibitors; Receptors, Calcitonin Gene-Related Peptide - physiology; Receptors, Drug - biosynthesis; Receptors, Drug - genetics; Sulfonylurea Receptors; Vasoconstriction; Vasoconstriction - drug effects; Vasoconstrictors; Vasodilation; Vasodilation - drug effects; Vasodilators
• ISSN: 0958-0670; 1469-445X
• DOI: 10.1113/expphysiol.2010.055822

Our study determines alterations in the vasoconstrictor response elicited by electric field stimulation (EFS) in mesenteric arteries from cirrhotic rats treated with CCl4, and how calcitonin gene‐related peptide (CGRP) participates in this response. Vasoconstriction induced by EFS was analysed in the absence and presence of the CGRP receptor antagonist CGRP(8–37) in arterial segments from control and cirrhotic rats. The vasodilator response to exogenous CGRP was tested in both groups of rats, and the interference of the guanylate cyclase inhibitor ODQ or the KATP channel blocker glibenclamide was analysed only in segments from cirrhotic rats. The vasodilator response to the KATP channel opener pinacidil and to 8‐bromo‐cyclic GMP was tested. The KATP currents were recorded using the patch‐clamp technique. Expression of receptor activity‐modifying protein 1 (RAMP1), calcitonin receptor‐like receptor, Kir 6.1 and sulfonylurea receptor 2B (SUR2B) was also analysed. Release of CGRP and cGMP was measured. The EFS‐elicited vasoconstriction was less in segments from cirrhotic rats. The presence of CGRP(8–37) increased the EFS‐induced response only in segments from cirrhotic rats. The CGRP‐induced vasodilatation was greater in segments from cirrhotic rats, and was inhibited by ODQ or glibenclamide. Both pinacidil and 8‐bromo‐cyclic GMP induced a stronger vasodilator response in segments from cirrhotic rats. Pinacidil induced greater KATP currents in cirrhotic myocytes. Expression of RAMP1, calcitonin receptor‐like receptor, Kir 6.1 and SUR2B was not modified by liver cirrhosis. Liver cirrhosis increased CGRP release, but did not modify cGMP formation. The decreased vasoconstrictor response to EFS in cirrhosis is mediated by increased vasodilator response to CGRP, as well as increased KATP channel gating. This effect of CGRP may play a role in the splanchnic vasodilatation present in liver cirrhosis.