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  • Title: Vasodilation mediated by angiotensin II type 2 receptor is impaired in afferent arterioles of young spontaneously hypertensive rats.
    Author: Endo Y, Arima S, Yaoita H, Tsunoda K, Omata K, Ito S.
    Journal: J Vasc Res; 1998; 35(6):421-7. PubMed ID: 9858867.
    Abstract:
    Renal vasoconstrictor action of angiotensin II (Ang II) is exaggerated in the spontaneously hypertensive rat (SHR) before development of hypertension. We have recently demonstrated that in the rabbit afferent arteriole (Af-Art) activation of the AT2 receptor causes vasodilation, which modulates the vasoconstrictor action of Ang II mediated by the AT1 receptor. In this study, we tested the hypothesis that vasoconstrictor action of Ang II is exaggerated in SHR Af-Arts due to an impaired function of the AT2 receptor before development of hypertension. Af-Arts were microdissected from the superficial cortex of 4- to 5-week-old SHR or age-matched Wistar Kyoto rats (WKY), and perfused at 60 mm Hg in vitro. Ang II (10(-11) to 10(-8) M) decreased the luminal diameter of Af-Arts of both strains in a dose-dependent manner. However, the constriction was stronger in SHR; at 10(-10) M, the diameter decreased by 34 +/- 4% in SHR (n = 6) compared to 18 +/- 3% in WKY (n = 6; p < 0.01). Pretreatment with PD123319 (PD), an AT2 receptor antagonist, significantly augmented Ang II-induced constriction in WKY but not SHR Af-Arts; at 10(-10) M, the diameter now decreased by 41 +/- 5 and 37 +/- 1% in SHR (n = 6) and WKY (n = 6), respectively. Thus, blockade of the AT2 receptor abolished the difference in Ang II action on Af-Arts between strains. Moreover, with the AT1 receptor blockade Ang II caused dose-dependent dilation of preconstricted Af-Arts only in WKY (27 +/- 5% at 10(-8) M, n = 5), and the dilation was abolished by simultaneous treatment with PD. In contrast, no such dilation was observed in SHR Af-Arts. These results suggest that activation of the AT2 receptor modulates AT1 receptor vasoconstriction in WKY Af-Arts, while impaired modulatory function of AT2 receptor may play a role in the exaggerated vasoconstrictor action of Ang II on the Af-Art of prehypertensive SHR.
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