Vascular hyporesponsiveness in aorta from portal hypertensive rats: possible sites of involvement.
Vascular hyporesponsiveness in portal hypertension has been proposed to be due to postreceptor defect. The present study was aimed to investigate possible sites of involvement in such hyporesponsiveness. Portal hypertension was induced by partial portal vein ligation (PVL). Concentration-response curves to KCI and phenylephrine in both groups showed that the Emax values were significantly lower in the PVL group. The EC50 values were not different between the two groups. In Ca++ free condition, phenylephrine induced a phasic contraction, which was significantly smaller in the aorta from PVL rats. Cumulative readdition of CaCl2 (1.0-2.5 mM) induced tension increases, which were all significantly lower in the PVL group. Basal contents of [3H]inositol phosphates in the aorta were similar between the two groups. Phenylephrine induced concentration-dependent increase of [3H]inositol phosphates in the aorta from both groups. The responses at 10(-8), 10(-7), 10(-6) and 10(-5) M were significantly smaller in the PVL group than in the sham-operated group. Both okadaic acid and phorbol 12,13-dibutyrate induced slowly developing contractile responses in the aorta. The responses were similar between the two groups at all time points. Our results suggested that in the aorta from PVL rats, vascular hyporesponsiveness was observed, together with decreased contractile responses due to: voltage- and receptor-dependent calcium influx as well as intracellular calcium release, and decreased receptor-coupled inositol phosphate formation. Contractile responses due to activation of protein kinase C or phosphatase inhibition were not impaired.
Huang
Y T
YT
Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Wang
G F
GF
Yang
M C
MC
Chang
S P
SP
Lin
H C
HC
Hong
C Y
CY
D000818:Animals; D001011:Aorta / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018924:Vascular Capacitance
D010656:Phenylephrine; D011189:Potassium Chloride