Insulin modulation of vascular reactivity is already impaired in prehypertensive spontaneously hypertensive rats.
Hyperinsulinemia reduces the vasoconstrictive response to norepinephrine in Wistar-Kyoto rats (WKY) but not in spontaneously hypertensive rats (SHR). It has been hypothesized that this difference in the vascular effect of insulin could be a hallmark of the hypertensive state. To test this hypothesis we studied SHR before (5 weeks old, n = 10) and after (15 weeks old, n = 10) the establishment of hypertension as well as two groups of age- and sex-matched WKY (5 weeks old, n = 14; 15 weeks old, n = 13). Blood pressure was significantly higher in SHR compared with WKY (181 +/- 5 versus 118 +/- 6 mm Hg, respectively, P < .001) in the 15-week-old rats but not in the 5-week-old rats (121 +/- 5 versus 117 +/- 3 mm Hg, P < NS). We tested vascular reactivity using increasing amounts of norepinephrine (from 10(-10) to 10(-5) mmol/L) on isolated aortic rings in control conditions and after 30 minutes of exposure to 715 pmol/L insulin. In WKY insulin reduced the vascular response to norepinephrine in both the 5-week-old (repeated-measures ANOVA with grouping factor: F = 2.443, P < .05) and 15-week-old (F = 9.667, P < .01) groups. In SHR at both ages insulin failed to modify the vascular response to norepinephrine (5 weeks: F = 0.107, P < NS; 15 weeks: F = 0.075, P < NS). Sodium nitroprusside was able to attenuate the vascular response to norepinephrine in WKY and SHR at 5 and 15 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
Lembo
G
G
IRCCS Sanatrix, Pozzilli, Italy.
Iaccarino
G
G
Vecchione
C
C
Rendina
V
V
Trimarco
B
B
D000367:Age Factors; D000818:Animals; D001011:Aorta / Q000503:physiopathology*; D001794:Blood Pressure; D004347:Drug Interactions; D006339:Heart Rate; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000187:drug effects*
D007328:Insulin; D009638:Norepinephrine