Local renin-angiotensin system in the microcirculation of spontaneously hypertensive rats.
We studied the local renin-angiotensin system in the microcirculation of cremaster muscle in spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto (WKY) controls. We used intravital microscopy in an original preparation of cremaster isolated from its normal blood supply and externally perfused with physiological solution, thus allowing the exclusion of circulating converting enzyme, circulating renin, and circulating angiotensinogen. We classified arterioles studied as second-, third-, and fourth-order, with mean diameters, respectively, of 67 +/- 6, 35 +/- 2, and 17 +/- 1 microns in WKY controls and 61 +/- 5, 34 +/- 2, and 16 +/- 1 microns in SHR. No difference between WKY controls and SHR was found for arteriolar vasoconstrictions in response to topical administration of 0.01 to 1 nmol/mL angiotensin II. Conversely, in response to 0.01 to 1 nmol/mL angiotensin I, significantly more arteriolar vasoconstriction was found in SHR cremaster muscle. In both strains, responses to angiotensin I were significantly inhibited by 10 nmol/mL of the angiotensin-converting enzyme inhibitor lisinopril. When angiotensinogen-rich, renin-free plasma containing 2.3 nmol/mL angiotensinogen was administered, almost no vasoconstriction was found in WKY controls, but significant constrictions were observed in SHR (23 +/- 4%, 30 +/- 5%, and 41 +/- 4% for second-, third-, and fourth-order arterioles, respectively). In SHR, vasoconstriction in response to angiotensinogen-rich, renin-free plasma was dose dependent, was inhibited by lisinopril, and was not found 24 hours after bilateral nephrectomy. Topical administration of 1.2 micrograms/mL renin did not induce arteriolar vasoconstriction in either WKY or SHR cremaster muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
Vicaut
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Laboratoire de Biophysique, Hôpital F. Widal, Paris, France.
Hou
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D000809:Angiotensins / Q000494:pharmacology; D000818:Animals; D006973:Hypertension / Q000503:physiopathology*; D017706:Lisinopril / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000503:physiopathology*; D009132:Muscles / Q000098:blood supply; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012083:Renin / Q000494:pharmacology; D012084:Renin-Angiotensin System / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects
D000809:Angiotensins; D017706:Lisinopril; D012083:Renin