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

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 paramete rs and Ang II-stimulated contraction were determined in small mesenteric ar teries from 6-week-old (phase of developing hypertension) and 21-week-old S HR (phase of established hypertension), compared with age-matched Wistar-Ky oto rats (WKY). To ascertain whether effects were specific for Ang II, cont ractile responses to another vasoactive agonist, vasopressin (AVP), were al so determined. Systolic blood pressure was measured in conscious rats by th e tail-cuff method. Segments of third-order mesenteric arteries (approximat e to 200 mu m in diameter and 2 mm in length) were mounted in a pressurized system with the intraluminal pressure maintained at 45 mm Hg. Blood pressu re was significantly increased in SHR (P < .001) and was higher in adult th an in young SHR (P < .001). Ang II dose-dependently increased contraction, with responses significantly greater (P < .05) in SHR than in age-matched W KY. SHR, in the early phase of hypertension, exhibited significantly augmen ted contractile responses (E-max = 70 +/- 5%), compared with SHR with estab lished hypertension (E-max = 33 +/- 5%). These effects were not generalized , as responses to AVP were not significantly different between young and ad ult SHR. Functional Ang II-elicited alterations were associated with struct ural modifications: 1-week-old SHR had smaller media to lumen ratio compare d with 21-week-old SHR (8.1% +/- 0.17% v 10.6% +/- 0.20%, P < .01). In youn g 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 w as increased in comparison to WKY rats, suggesting mild hypertrophic remode ling (growth index -1.0% v 15.2%, young v adult). In conclusion, the presen t study demonstrates that in SHR with early hypertension and slight medial thickening, Ang II-mediated vascular contractile responsiveness is signific antly augmented compared with SHR with established hypertension and more se vere vascular structural changes. These findings indicate attenuation, as h ypertension progresses, of the initially enhanced vascular reactivity to An g II that is present during the development of hypertension in SHR (C) 1999 American Journal of Hypertension, Ltd.