Prostaglandin H2 and thromboxane A2 are contractile factors in intrarenal arteries of spontaneously hypertensive rats.

Abstract

Vascular resistance is increased in the kidneys of spontaneously hypertensive rats (SHR).Imbalanced production of relaxing and contracting factors by the endothelium may play an important role in both the initiation and the maintenance of the abnormal vasoconstriction characteristically seen in humans with essential hypertension and in genetic models of hypertension in animals. 4-5 Endothelium-dependent relaxations are impaired in the aorta and mesenteric resistance arteries of spontaneously hypertensive rats (SHR).6 -11 In both vessels, the impaired relaxations result from enhanced production of a cyclooxygenasedependent endothelium-derived contracting factor (EDCF) that antagonizes the relaxing properties of endothelium-derived nitric oxide.6 -11 More than one EDCF may be produced in SHR arteries.12 Two recent reports suggest that the EDCF produced by the SHR aorta may be prostaglandin H 2 (PGH 2 ) or thromboxane A 2 (TXA,).10 - 11From the Department of Medicine, Division of Nephrology and Hypertension, University of Kansas Medical Center, Kansas City, Kan. The objectives of the studies described in this report were twofold: 1) to determine if endothelium-mediated relaxations were impaired in resistance arteries isolated from kidneys of young SHR and 2) to characterize the nature of the factor(s) that promotes enhanced constriction in resistance arteries. EDCFs may function by inactivating the endothelium-derived relaxing factor nitric oxide, 13 by direct activation of contractile responses in vascular smooth muscle cells, or by a combination of the two mechanisms. MethodsMale, 5-6-week-old SHR and normotensive WistarKyoto (WKY) rats were obtained from Harlan Laboratories, Boston, Mass. The rats were maintained four per cage at constant temperature (24±1°C), with a 12-hour dark/light cycle and standard rat chow. All procedures followed were in accordance with institutional guidelines. Systolic blood pressure was measured in conscious, prewarmed, restrained rats by the tail-cuff method by using plethysmography and a physiograph recorder (model 11 TC, Innovators in Instrumentation, Woodland Hills, Calif.). Vessel PreparationRats were anesthetized with ether. The abdominal aorta was cannulated to enable in situ perfusion of the aorta and renal and superior mesenteric arteries with

Magnesium Removal Impairs the Regulatory Role of Rat Endothelium.

“…Still, the response to acetylcholine seems to be incompatible with the finding of previous studies that the release of EDRF is diminished in animal models of hypertension. However, the impaired relaxation by acetylcholine is not responsible for the decreased release of EDRF, but it is responsible for the increased formation of endothelium-derived contracting factors that may play a part in animals older than those examined in the present study (33,34). The increase in the release of EDRF might be counterbalanced by a decrease in efficacy of acetylcholine due to a conformational change of the receptor in Mg-free solution (2, 35).…”

Cyclooxygenase-derived products modulate the increased intrahepatic resistance of cirrhotic rat livers

“…This is not unique to the cirrhotic liver, because an increased release of vasoconstrictive prostanoids has been reported in other situations in which there is an impaired endothelial-dependent vascular relaxation, such as in mesenteric arteries and intrarenal arteries of spontaneously hypertensive rats. 33,34 The nature of the putative COX-dependent vasoconstrictor responsible for such an effect is not completely defined. The results of our study strongly suggest that TXA 2 may be involved, because methoxamine induced a significantly greater increase of this vasoconstrictor prostanoid in cirrhotic than in control livers.…”

Low Sodium Modifies the Vascular Effects of Angiotensin-Converting Enzyme Inhibitor Therapy in Healthy Rats

“…Interestingly, COX-inhibition with indomethacin acutely normalized this impairment. Evidence from studies with spontaneously hypertensive rats using indomethacin and PGH 2 /TXA 2 receptor blockers (e.g., SQ 29,548) indicate that endothelium-derived PGH 2 and TXA 2 are contractile factors in intrarenal arteries that may underlie impaired relaxation to ACh (Dai et al, 1992;FuXiang et al, 1992). Numerous studies have addressed the role of prostaglandins during changes in dietary sodium (Hocherl et al, 2002), but the impact on small vessels is less well known.…”