Hyposensitivity to nerve stimulation in portal hypertensive rats: role of nitric oxide.
Portal hypertension goes along with vascular hyporeactivity, partly mediated by nitric oxide (NO). Interactions between the adrenergic nervous system and NO in portal hypertension are undetermined. We tested (1) whether superior mesenteric arterial beds of portal hypertensive rats have an altered sensitivity to periarterial nerve stimulation (PNS) and (2) the role of NO in modulating nerve-stimulated responses. Vasopressor responses to PNS (Hz, 2-32) were similar in preparations of partial portal vein-ligated (PVL, n = 12) and control (CON, n = 12) rats (60.0 +/- 6.7 and 47.8 +/- 6.1 CmH2O respectively) for 24 Hz (NS), but sensitivity of vessels of portal hypertensive animals displayed a significant rightward shift [Hz needed for 50% of maximal response (HZ50) being 15.5 +/- 0.4 and 12.9 +/- 0.6 for PVL and CON respectively, P < 0.001]. NO formation inhibition by N omega-nitro-L-arginine (10(-4) mol L-1) significantly increased responses to PNS (P < 0.05), the absolute values for 24 Hz being 101.4 +/- 11.7 cmH2O for PVL (n = 8) and 86.4 +/- 11.4 cmH2O for CON (n = 7) (NS). NO formation inhibition reversed the hyposensitivity in preparations of PVL, Hz50 being 13.9 +/- 0.5 and 13.2 +/- 0.2 for PVL and CON respectively (NS). Adrenergic receptor antagonism with prazosin (10(-7) mol L-1) and yohimbine (10(-6) mol L-1) inhibited PNS-mediated vasopressor reactivity (n = 6 per group, P < 0.001), confirming the nervous origin of vasoconstrictor responses. It is concluded that (1) portal hypertension goes along with a significant hyposensitivity to PNS and (2) this hyposensitivity is reversed by NO-formation inhibition
Sieber
C C
CC
Division of Gastroenterology, University Hospital, Basle, Switzerland.
Sumanovski
L T
LT
Moll-Kaufmann
C
C
Stalder
G A
GA
D000818:Animals; D004558:Electric Stimulation; D006975:Hypertension, Portal / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D010525:Peripheral Nerves / Q000502:physiology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects
D019335:Nitroarginine; D009569:Nitric Oxide; D011224:Prazosin