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.
Boussairi
E H
EH
Department of Physiology and Clinical Pharmacology, Centre National de la Recherche Scientifique, Faculty of Pharmacy, Lyon, France.
Sacquet
J
J
Sassard
J
J
Benzoni
D
D
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