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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

The aorta is composed of various constituents with different mechanical properties. This heterogeneous structure implies non-uniform deformation in the aorta, which could affect local cell functions. The present study investigates 3D strains of the aorta at a cell scale induced by intraluminal pressurization. After resected mouse, thoracic aortas were stretched to their in vivo length, and the aortas were pressurized at 15, 40, 80, 120, and 160 mmHg. Images of autofluorescent light of elastin were captured under a two-photon microscope. From the movement of markers in elastic laminas (ELs) created by photo-bleaching, 3D strains (ε θθ , ε zz , ε rr , ε rθ , ε rz , ε θz) between two neighboring ELs in the circumferential (θ), longitudinal (z), and radial (r) directions with reference to the dimensions at 15 mmHg were calculated. The results demonstrated that the average of shear strain ε rθ was almost 0 in a physiological pressure range (from 80 to 120 mmHg) with an absolute value |ε rθ | changing approximately by 5%. This indicates that ELs experience radial-circumferential shear at the cell scale, but not at the whole tissue scale. The normal strains in the circumferential ε θθ and longitudinal direction ε zz were positive but that in the radial direction ε rr was almost 0, which demonstrates that aortic tissue is not an incompressible material. The first principal direction in the radial-circumferential plane was 29° ± 13° from the circumferential direction. We show that the aorta is not simply stretched in the circumferential direction during pressurization and that cells in the aorta undergo complex deformations by nature.

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