Premium
Role of cyclic guanosine monophosphate and K + channels as mediators of the mesenteric vascular hyporesponsiveness in portal hypertensive rats
Author(s) -
Atucha Noemí M.,
Ortíz M. Clara,
Fortepiani Lourdes A.,
Ruiz Francisco M.,
Martínez Concepción,
GarcíaEstañ Joaquín
Publication year - 1998
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510270402
Subject(s) - methoxamine , medicine , glibenclamide , endocrinology , potassium channel , portal hypertension , vasodilation , cyclic guanosine monophosphate , mesenteric arteries , tetraethylammonium , potassium channel blocker , nitric oxide , charybdotoxin , chemistry , potassium , artery , receptor , cirrhosis , organic chemistry , diabetes mellitus , agonist
The mechanisms mediating the hyporesponsiveness to vasoconstrictors in portal hypertension are not completely established. In the present study, we evaluated the role of cyclic guanosine monophosphate (cGMP) and potassium channels as contributors to the pressor hyporesponsiveness to methoxamine (MTX) of the mesenteric vascular bed of portal vein‐ligated (PVL) hypertensive rats. In basal conditions, and compared with sham‐operated control rat (SHAM) vessels, PVL preparations showed a blunted pressor response (maximum: 39.3 ± 6.1 vs. 94.5 ± 8.9 mm Hg), which increased by pretreatment with methylene blue (MB), a guanylate cyclase inhibitor (118.7 ± 8.9 vs. 152.0 ± 10.0, respectively), and even more with the nitric oxide (NO) synthesis inhibitor N ω ‐nitro‐ l ‐arginine (NNA) (159.9 ± 7.4 vs. 194.1 ± 5.7, respectively), suggesting that NO acts through cGMP‐dependent and independent mechanisms. In all cases, however, the pressor responses of PVL vessels were lower than those of SHAM. Pretreatment of the vessels with the potassium channel inhibitors, tetraethylammonium (TEA), glibenclamide (GLB), or charybdotoxin (CHX), did not improve the reduced pressor responses of the PVL rats. However, when the preparations were simultaneously pretreated with MB and TEA or with NNA and TEA, the pressor responses were potentiated with respect to groups treated with MB or NNA alone, and the differences between PVL and SHAM vessels were completely corrected. These data suggest that both NO and potassium channels mediate the vascular hyporesponsiveness to methoxamine of the PVL mesenteric vasculature. Our results also disclose that NO blunts the pressor response of the PVL vessels by a dual mechanism of action, through activation of potassium channels and through the formation of cGMP. Finally, the NO‐independent component mediated by potassium channels can be only seen when the main cGMP‐NO component is inactivated. In conclusion, both cGMP and potassium channels mediate the vascular hyporesponsiveness to MTX of the mesenteric bed of portal hypertensive rats.