Thromboxane A2-prostaglandin H2 and renovascular hypertension in rats.
To evaluate the contribution of thromboxane (Tx) A2-prostaglandin (PG) H2 in two-kidney, one-clip Goldblatt hypertension (GH), 26 GH rats were chronically treated (GHT) with a specific TxA2-PGH2 receptor antagonist, CGS-22652 (30 mg.kg-1.24 h-1 sc); 28 others as well as 17 sham-clipped (SC) rats received vehicle. Twelve GH and 3 GHT rats developed malignant hypertension and died. After 6 wk of treatment, GH rats exhibited higher mean blood pressure (BP; 189 +/- 3 vs. 118 +/- 2 mmHg) and an increased vascular reactivity to the main pressor agents compared with SC rats. Chronic TxA2-PGH2 receptor blockade lowered mean BP in 13 GHT rats (125 +/- 3 mmHg) and decreased their vascular reactivity compared with GH rats. However, 10 GHT rats remained hypertensive (190 +/- 9 mmHg) and differed from the former by an increased vascular reactivity to vasopressin. It is concluded that renal artery clipping induces either benign or malignant hypertension. In benign forms, TxA2-PGH2 blockade normalizes BP through decreasing the vascular responsiveness to the main pressor agents. In malignant forms, it limits the elevation of BP and markedly reduces mortality.
Department of Physiology and Clinical Pharmacology, Centre National de la Recherche Scientifique, Faculty of Pharmacy, Lyon, France.
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Boussairi
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Sacquet
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Sassard
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Benzoni
D000375:Aging / Q000502:physiology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D002210:Caprylates / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003971:Diastole; D005665:Furosemide / Q000494:pharmacology; D006321:Heart / Q000033:anatomy & histology; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D007668:Kidney / Q000033:anatomy & histology; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D009929:Organ Size; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D012016:Reference Values; D013449:Sulfonamides / Q000494:pharmacology*; D013599:Systole; D013997:Time Factors; D014661:Vasoconstriction
D002210:Caprylates; D016861:Cyclooxygenase Inhibitors; D017482:Receptors, Thromboxane; D013449:Sulfonamides; D000804:Angiotensin II; D001127:Arginine Vasopressin; C078274:CGS 22652; D009599:Nitroprusside; D010656:Phenylephrine; D005665:Furosemide; D009638:Norepinephrine