BACKGROUND/AIMS: Hyporesponsiveness to vasoconstrictors in portal hypertension has been shown to involve increased production of nitric oxide in large arteries in vitro. Small arteries (diameter 50-500 microns) are partly responsible for peripheral resistance and probably have different regulatory mechanisms from large arteries. The purpose of this study was to investigate the hyporeactivity of small mesenteric resistance arteries in portal hypertensive rats and to determine the role of nitric oxide and prostaglandins in this hyporesponsiveness. METHODS: Third branch mesenteric arteries from normal and portal hypertensive rats obtained by portal vein ligation were isolated and suspended in myographs for isometric tension recording. Reactivity to vasoconstrictors was assessed by dose-responses to phenylephrine (Phe 10(-8) to 10(-3) M) and by potassium chloride (KCl 45 mM). Acetylcholine (Ach 10(-5) M) was administered in pre-contracted KCl 45 mM arterial rings to evaluate endothelium-dependent relaxation. Pre-incubations with N-nitro-L-arginine (L-NNA 10(-4) M, a specific inhibitor of nitric oxide synthase, or with indomethacin (10(-5) M), a specific inhibitor of cyclo-oxygenase, were performed to compare the individual roles of nitric oxide and prostaglandins in KCl 45 mM-induced contractions. RESULTS: Impaired responses to Phe (3731 +/- 851 microN and 5971 +/- 745 microN, respectively; p < 0.05) and to KCl (2197 +/- 251 vs 2804 +/- 222 microN, respectively; p < 0.05) were observed in mesenteric resistance arterial rings from portal hypertensive rats compared to rings from normal rats. Ach-dependent relaxation did not significantly differ between normal (-25.7 +/- 5.1%) and portal hypertensive (-17.3 +/- 3.3%) rats. Indomethacin induced a similar significant increase in KCl-induced contraction in normal (3472 +/- 400 microN) and portal hypertensive (3432 +/- 654 rats. Nitric oxide synthesis inhibition had no effect in normal rats (3032 +/- 368 microN) but significantly increased KCl-induced contraction in portal hypertensive rats (3331 +/- 551 microN). CONCLUSION: These results demonstrate the existence of a hyporesponsiveness to vasoconstrictors in small mesenteric resistance arteries of portal hypertensive rats, which seems to be due to increased production of nitric oxide.
BACKGROUND/AIMS: Hyporesponsiveness to vasoconstrictors in portal hypertension has been shown to involve increased production of nitric oxide in large arteries in vitro. Small arteries (diameter 50-500 microns) are partly responsible for peripheral resistance and probably have different regulatory mechanisms from large arteries. The purpose of this study was to investigate the hyporeactivity of small mesenteric resistance arteries in portal hypertensiverats and to determine the role of nitric oxide and prostaglandins in this hyporesponsiveness. METHODS: Third branch mesenteric arteries from normal and portal hypertensiverats obtained by portal vein ligation were isolated and suspended in myographs for isometric tension recording. Reactivity to vasoconstrictors was assessed by dose-responses to phenylephrine (Phe 10(-8) to 10(-3) M) and by potassium chloride (KCl 45 mM). Acetylcholine (Ach 10(-5) M) was administered in pre-contracted KCl 45 mM arterial rings to evaluate endothelium-dependent relaxation. Pre-incubations with N-nitro-L-arginine (L-NNA 10(-4) M, a specific inhibitor of nitric oxide synthase, or with indomethacin (10(-5) M), a specific inhibitor of cyclo-oxygenase, were performed to compare the individual roles of nitric oxide and prostaglandins in KCl 45 mM-induced contractions. RESULTS: Impaired responses to Phe (3731 +/- 851 microN and 5971 +/- 745 microN, respectively; p < 0.05) and to KCl (2197 +/- 251 vs 2804 +/- 222 microN, respectively; p < 0.05) were observed in mesenteric resistance arterial rings from portal hypertensiverats compared to rings from normal rats. Ach-dependent relaxation did not significantly differ between normal (-25.7 +/- 5.1%) and portal hypertensive (-17.3 +/- 3.3%) rats. Indomethacin induced a similar significant increase in KCl-induced contraction in normal (3472 +/- 400 microN) and portal hypertensive (3432 +/- 654 rats. Nitric oxide synthesis inhibition had no effect in normal rats (3032 +/- 368 microN) but significantly increased KCl-induced contraction in portal hypertensiverats (3331 +/- 551 microN). CONCLUSION: These results demonstrate the existence of a hyporesponsiveness to vasoconstrictors in small mesenteric resistance arteries of portal hypertensiverats, which seems to be due to increased production of nitric oxide.
Authors: M Bolognesi; D Sacerdoti; M Di Pascoli; P Angeli; S Quarta; A Sticca; P Pontisso; C Merkel; A Gatta Journal: Gut Date: 2005-06-10 Impact factor: 23.059
Authors: Victor M Pulgar; Anne B Jeffers; Hanadi M Rashad; Debra I Diz; Azeez A Aileru Journal: J Cardiovasc Pharmacol Date: 2013-08 Impact factor: 3.105