The role of thromboxane A2 in the altered microvascular reactivity in two-kidney, one-clip hypertension.
To investigate the nature of the arachidonic acid metabolite involved in the altered reactivity of microvessels of two-kidney, one-clip hypertensive rats and the possible contribution of this product to the elevated blood pressure levels found in two-kidney, one-clip hypertension, mesenteric arterioles either perfused in vitro or studied in vivo were used along with blood pressure determinations. The decreased response to acetylcholine observed was normalized by ridogrel, a thromboxane A2 receptor antagonist, and dazoxiben, a thromboxane A2 synthase inhibitor. The smooth muscle response to nitric oxide, tested with sodium nitroprusside, was unaltered in two-kidney, one-clip hypertensive microvessels. Neither ridogrel nor dazoxiben modified the response to this vasodilator. In contrast, the potentiated response to noradrenaline was corrected by ridogrel and dazoxiben in vitro but not in vivo. Noradrenaline and acetylcholine increased the release of thromboxane A2 from the mesenteric microvessels of two-kidney, one-clip hypertensive rats. Ridogrel and dazoxiben decreased but did not normalize the elevated blood pressure of hypertensive rats. Based on these results, we concluded that: 1) the decreased responsiveness of smooth muscle to acetylcholine resulted from an increase in thromboxane A2 formation rather than a decrease in sensitivity to nitric oxide; 2) thromboxane A2 contributes to the increased noradrenaline response in mesenteric microvessels perfused in vitro while in in vivo other blood borne vasoactive agents may also be involved since the potentiated noradrenaline response was not corrected by inhibiting thromboxane A2 synthesis or receptors; 3) in addition to thromboxane A2, another as yet unidentified factor, may contribute to the elevated blood pressure in two-kidney, one-clip hypertension.
Carvalho
M H
MH
Dept. of Pharmacology, University of Sao Paulo, Brazil.
Fortes
Z B
ZB
Nigro
D
D
Oliveira
M A
MA
Scivoletto
R
R
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008643:Mesentery / Q000098:blood supply; D008833:Microcirculation; D009569:Nitric Oxide / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D010421:Pentanoic Acids / Q000494:pharmacology; D010477:Perfusion; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D012079:Renal Circulation; D013928:Thromboxane A2 / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014655:Vascular Resistance / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007093:Imidazoles; D010421:Pentanoic Acids; D011725:Pyridines; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D014662:Vasoconstrictor Agents; C029166:dazoxiben; D009599:Nitroprusside; D009569:Nitric Oxide; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D013930:Thromboxane-A Synthase; C060219:ridogrel