Exaggerated vascular response due to endothelial dysfunction and role of the renin-angiotensin system at early stage of renal hypertension in rats.

Abstract

We investigated whether endothelial dysfunction might contribute to the exaggerated vasoconstriction that was induced by the administration of norepinephrine at the early stage of one-kidney, one-clip renal hypertension (1K1C) in rats. We also studied the role of the renin-angiotensin system in this phenomenon. Male Wistar rats were killed 48 hours after the induction of renal artery stenosis or sham operation, and ring preparations of the thoracic aorta were obtained. The isometric contraction and relaxation of aortic strips produced by norepinephrine and acetylcholine, respectively, were recorded with a force-displacement transducer. The aorta of 1K1C rats showed a significantly (P<.05) exaggerated contractile response to norepinephrine as compared with that of control rats. Rubbing the endothelium and treatment with methylene blue or N0-monomethyl L-arginine acetate augmented the contractile responses to norepinephrine to a greater extent in Although an increased vascular reactivity to vaso-L.1 constrictor substances has been observed both in clinical hypertension",2 and in animal models of hypertension,3-9 the mechanisms are not completely understood. Folkow et al10 suggest that this hyperresponsiveness in hypertension is due to vascular wall hypertrophy or medial hypertrophy that results in an increased vessel wall to lumen ratio. Findings of other investigators4,5"11 indicate that such mechanisms are not the only explanation. For instance, Prewitt et al"l reported that no vascular wall hypertrophy was observed in resistance vessels of one-kidney, one-clip renal hypertensive (iKiC) rats, despite a structural reduction in the size of the lumen. Others45 have reported that an exaggerated pressor response and increased sensitivity (change in threshold) to norepinephrine occur in rabbits with renal artery stenosis at an early stage, even before the onset of hypertension. These studies4,5"11 indicate that the exaggerated pressor response may be due to some alteration in the responsiveness of the vessels without hypertrophy of the vascular wall and suggest that the responsiveness of the vascular smooth muscle cells itself may be enhanced. However, confirmatory evidence is lacking.Received February 18, 1993; accepted October 8, 1993 Our objective was to determine the role of depressed synthesis and/or release of EDRF on the exaggerated vasoconstrictive response to norepinephrine at the early stage of hypertension before the development of vascular wall hypertrophy or an increased vascular wall to lumen ratio. The present study was designed to clarify the role of the renin-angiotensin system in endothelial by guest on

Production of Nitric Oxide, but Not Prostacyclin, Is Reduced in Klotho Mice

“…For vasoconstriction measurements, the maximum response was taken to be the maximum force (mg) induced by norepinephrine (7,8). The vasodilator response to each dose of drug is expressed as a percent of the level that preceded the preconstriction induced by norepinephrine (7,8).…”

Selective Angiotensin Receptor Antagonism with Valsartan Decreases Arterial Stiffness Independently of Blood Pressure Lowering in Hypertensive Patients

“…These major cardiovascular effects are mediated by the type 1 angiotensin II receptor (ATR). We have previously reported that angiotensin II receptor blockade protects endothelial function in renal hypertension (6), and type 1 angiotensin II receptor blockers (ARB) have now been widely used as antihypertensive drugs with the expectation of a vascular protective effect (7).…”

Effect of Cerivastatin on Endothelial Dysfunction and Aortic CD36 Expression in Diabetic Hyperlipidemic Rats

“…To confirm that the vascular smooth muscle cells were intact, the vasodilator response to sodium nitroprusside (10 10 to 10 7 mol/l) was determined. The amount of superoxide necessary to shorten the half-life of endothelium-derived NO was also evaluated by administering lecithinized superoxide dismutase (lecithinized SOD) (0.25 to 4.0 units/l) (19,20). Acetylcholine (Sigma Chemical Co., St. Louis, USA) and LNAME (Calbiochem Co., La Jolla, USA) were dissolved in Krebs bicarbonate solution.…”

“…The maximum vasodilator response was defined as the level of vasodilation that preceded the preconstriction induced by norepinephrine. The response to each dose of drug is expressed as a percent of the maximum vasodilation as described previously (19,20).…”