Modulation of splanchnic vascular sensitivity to angiotensin II.
We studied whether the diminished splanchnic vascular response to angiotensin II infusion in portal hypertension could be related to elevated levels of prostacyclin (PGI2). The changes in superior mesenteric artery resistance (RSMA) and systemic vascular resistance (RSYS) during angiotensin II infusion were measured by Doppler flow probe in normal rabbits (NL) and portal hypertensive rabbits (PHT), and in NL and PHT after cyclooxygenase blockade (CO) and after CO and during continuous PGI2 infusion at 300 ng/kg/min. Angiotensin II infusion in NL caused a disproportionately greater increase in RSMA than in RSYS (p less than 0.01). In PHT, angiotensin II response of RSMA was reduced from NL (p less than 0.05). CO dramatically improved the splanchnic response to angiotensin II in PHT animals, but did not significantly alter the RSMA response in NL. PGI2 in NL, NL + CO, and PHT + CO quantitatively established the splanchnic vascular hyporesponsiveness to angiotensin II seen in PHT. We conclude that PGI2 will directly diminish splanchnic response to angiotensin II in NL, and CO will ablate differences in splanchnic response between NL and PHT to angiotensin II. This strongly implies that much of the observed decrease in angiotensin II response in PHT is mediated by PGI2 and that the differences between NL and PHT vascular response is in part the result of circulating vasodilatory substances.
Wu
Y P
YP
Johns Hopkins Hospital, Baltimore, MD 21205.
Li
S S
SS
Campbell
K A
KA
Sitzmann
J V
JV
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D016861:Cyclooxygenase Inhibitors; D004195:Disease Models, Animal; D011464:Epoprostenol / Q000494:pharmacology*; D006975:Hypertension, Portal / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology; D011817:Rabbits; D013152:Splanchnic Circulation / Q000187:drug effects* / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
D016861:Cyclooxygenase Inhibitors; D000804:Angiotensin II; D011464:Epoprostenol; D007213:Indomethacin