Effects of saralasin on arterial compliance in normotensive and hypertensive rats. Role of endothelium.
We used an experimental model of in situ isolated carotid arteries to clarify the participation of angiotensin II (Ang II) in the mechanical properties of the arterial wall in 12-week-old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs). The effects of local incubation with saralasin ([Sar1,Thr8]Ang II, 10(-6) M) on carotid compliance were compared with the effects of endothelium removal and with those of total abolition of vasomotor tone with potassium cyanide (0.1 mg/ml). Operating carotid compliance measured for pressure values close to the mean arterial pressure of each group was (mean +/- SD) 12.6 +/- 2.9 x 10(-3) microliters/mm Hg.mm vessel in WKY rats and 8.2 +/- 1.6 x 10(-3) microliters/mm Hg.mm vessel in SHRs (p less than 0.001). With intact endothelium, local incubation with saralasin increased carotid compliance by 24% in WKY rats and 23% in SHRs relative to control values (p less than 0.05 and p less than 0.001, respectively). Endothelium removal induced significant increases in carotid compliance in WKY rats (17%, p less than 0.01) and in SHRs (33%, p less than 0.001). After endothelium removal, saralasin induced significant further carotid compliance increases in both strains (+18%, p less than 0.001, and +11%, p less than 0.01, in WKY rats and SHRs, respectively). After potassium cyanide poisoning, carotid compliance did not increase further relative to saralasin values in both strains with or without endothelium. These findings suggest that Ang II receptors play a major role in the control of the basal vasomotor tone of large arteries in both normotensive and hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Institut National de la Santé et de la Recherche Médicale, Unit 141, Hôpital Lariboisière, Paris, France.
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Stefas
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Levy
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001158:Arteries / Q000503:physiopathology*; D003187:Compliance / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology*; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D011190:Potassium Cyanide / Q000506:poisoning; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011945:Receptors, Angiotensin / Q000502:physiology; D012504:Saralasin / Q000494:pharmacology*
D011945:Receptors, Angiotensin; D000804:Angiotensin II; D012504:Saralasin; D011190:Potassium Cyanide