title: Intravital Förster resonance energy transfer imaging reveals elevated [Ca2+]i and enhanced sympathetic tone in femoral arteries of angiotensin II-infused hypertensive biosensor mice.
abstract: Artery narrowing in hypertension can only result from structural remodelling of the artery, or increased smooth muscle contraction. The latter may occur with, or without, increases in [Ca(2+)]i. Here, we sought to measure, in living hypertensive mice, possible changes in artery dimensions and/or [Ca(2+)]i, and to determine some of the mechanisms involved. Ca(2+)/calmodulin biosensor (Förster resonance energy transfer-based) mice were made hypertensive by s.c. infusion of angiotensin II (Ang II, 400 ng kg(-1) min(-1), 2-3 weeks). Intravital fluorescence microscopy was used to determine [Ca(2+)]i and outer diameter of surgically exposed, intact femoral artery (FA) of anaesthetized mice. Active contractile FA 'tone' was calculated from the basal-state diameter and the passive (i.e. Ca(2+)-free) diameter (PD). Compared to saline control, FAs of Ang II-infused mice had (1) ∼21% higher active tone and (2) ∼78 nm higher smooth muscle [Ca(2+)]i, but (3) the same PDs. The local Ang II receptor (AT1R) blocker losartan had negligible effect on tone or [Ca(2+)]i in control FAs, but reduced the basal tone by ∼9% in Ang II FAs. Both i.v. hexamethonium and locally applied prazosin abolished the difference in FA tone and [Ca(2+)]i, suggesting a dominant role of sympathetic nerve activity (SNA). Changes in diameter and [Ca(2+)]i in response to locally applied phenylephrine, Ang II, arginine vasopressin, elevated [K(+)]o and acetylcholine were not altered. In summary, FAs of living Ang II hypertensive mice have higher [Ca(2+)]i, and are more constricted, due, primarily, to elevated SNA and some increased arterial AT1R activation. Evidence of altered artery reactivity or remodeling was not found.
authors: J. Zhang: Department of Physiology, University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, USA. jzhan002@umaryland.edu.
authors: Youhua
authors: Y
authors: Wang
authors: Ling
authors: L
authors: Chen
authors: W Gil
authors: WG
authors: Wier
authors: Jin
authors: J
authors: Zhang
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D015374:Biosensing Techniques; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002147:Calmodulin / Q000235:genetics / Q000378:metabolism; D005263:Femoral Artery / Q000294:innervation / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D031541:Fluorescence Resonance Energy Transfer; D018738:Hexamethonium / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007262:Infusions, Intravenous; D019808:Losartan / Q000494:pharmacology; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000503:physiopathology; D011224:Prazosin / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects; D014661:Vasoconstriction
chemical_list: D000959:Antihypertensive Agents; D002147:Calmodulin; D000804:Angiotensin II; D018738:Hexamethonium; D019808:Losartan; D002118:Calcium; D011224:Prazosin
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