Prostanoids, but not nitric oxide, counterregulate angiotensin II mediated vasoconstriction in vivo.
To evaluate the modulating effects of nitric oxide and prostanoids during angiotensin II-mediated vasoconstriction, male Wistar rats (n=25) were infused with increasing doses of angiotensin II following pretreatment with the cyclooxygenase inhibitor indomethacin, the nitric oxide-synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) plus sodium nitroprusside to restore mean arterial blood pressure, or saline. Hemodynamics were studied with the radioactive microsphere method. Indomethacin did not alter systemic or regional hemodynamics. L-NAME+sodium nitroprusside reduced cardiac output, as well as systemic and renal vascular conductance. Angiotensin II increased mean arterial blood pressure and heart rate, and decreased systemic vascular conductance as well as vascular conductance in gastrointestinal tract, kidney, skeletal muscle, skin, mesentery+pancreas, spleen and adrenal. Indomethacin enhanced the angiotensin II-mediated effects in all vascular beds, whereas L-NAME+sodium nitroprusside enhanced its effect in mesentery+pancreas only. In conclusion, vasodilator prostanoids, but not nitric oxide, counterregulate angiotensin II-mediated vasoconstriction in vivo.
Schuijt
M P
MP
Department of Pharmacology, Erasmus University Rotterdam, Room EE1418b, Dr. Molewaterplein 50, 3015 GE, Rotterdam, Netherlands.
de Vries
R
R
Saxena
P R
PR
Jan Danser
A H
AH
D000311:Adrenal Glands / Q000098:blood supply; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007422:Intestines / Q000098:blood supply; D007668:Kidney / Q000098:blood supply; D008297:Male; D008643:Mesentery / Q000098:blood supply; D018482:Muscle, Skeletal / Q000098:blood supply; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010179:Pancreas / Q000098:blood supply; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply; D013154:Spleen / Q000098:blood supply; D013270:Stomach / Q000098:blood supply; D014661:Vasoconstriction / Q000187:drug effects*
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D011453:Prostaglandins; D000804:Angiotensin II; D009599:Nitroprusside; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin