Altered angiotensin II-induced small artery contraction during the development of hypertension in spontaneously hypertensive rats

Abstract

This study assessed whether the angiotensin-II (Ang II)-induced contractile responsiveness of resistance arteries is altered during the development of hypertension in spontaneously hypertensive rats (SHR). Structural parameters and Ang II-stimulated contraction were determined in small mesenteric arteries from 6-week-old (phase of developing hypertension) and 21-week-old SHR (phase of established hypertension), compared with age-matched Wistar-Kyoto rats (WKY). To ascertain whether effects were specific for Ang II, contractile responses to another vasoactive agonist, vasopressin (AVP), were also determined. Systolic blood pressure was measured in conscious rats by the tail-cuff method. Segments of third-order mesenteric arteries (≈200 μm in diameter and 2 mm in length) were mounted in a pressurized system with the intraluminal pressure maintained at 45 mm Hg. Blood pressure was significantly increased in SHR ( P < .001) and was higher in adult than in young SHR ( P < .001). Ang II dose-dependently increased contraction, with responses significantly greater ( P < .05) in SHR than in age-matched WKY. SHR, in the early phase of hypertension, exhibited significantly augmented contractile responses (E max = 70 ± 5%), compared with SHR with established hypertension (E max = 33 ± 5%). These effects were not generalized, as responses to AVP were not significantly different between young and adult SHR. Functional Ang II-elicited alterations were associated with structural modifications: 6-week-old SHR had smaller media to lumen ratio compared with 21-week-old SHR (8.1% ± 0.17% v 10.6% ± 0.20%, P < .01). In young SHR vessels the media cross-sectional area was unchanged relative to age-matched WKY rats, suggesting eutrophic remodeling (remodeling index 101.4% v 93.3% young v adult), whereas the cross-sectional area of adult vessels was increased in comparison to WKY rats, suggesting mild hypertrophic remodeling (growth index −1.0% v 15.2%, young v adult). In conclusion, the present study demonstrates that in SHR with early hypertension and slight medial thickening, Ang II-mediated vascular contractile responsiveness is significantly augmented compared with SHR with established hypertension and more severe vascular structural changes. These findings indicate attenuation, as hypertension progresses, of the initially enhanced vascular reactivity to Ang II that is present during the development of hypertension in SHR