Decreased arteriolar endothelium-derived relaxing factor production during the development of genetic hypertension

In the present study, basal and stimulated production of endothelium-derived relaxing factor (EDRF) were examined in young (4-5 week-old) and mature (10-12 week-old) spontaneously hypertensive rats (SHR) and were compared with those of age-matched Wistar Kyoto (WKY) normotensive rats. Nw-nitro-L-arginine methyl ester (L-NAME) was used as a probe for basal EDRF production in vivo. We also determined the dose-response effects of acetylcholine (Ach, 10(-9)-10(-5) M), sodium nitroprusside (NP, 10(-9)-10(-5) M), and norepinephrine (NE, 3 x 10(-10)-10(-6) M), on third-order arterioles (3A) in the two age groups. Relaxation of 3A vessels in response to Ach was significantly lower (p < 0.01) in mature SHR than in WKY rats. No significant differences were observed in responses to Ach in young animals or in responses to NP in either age groups. Preincubation with L-NAME (2 x 10(-4) M) shifted the dose-response curves of NE to the left in mature WKY rats (n = 6), but not in mature SHR (n = 6). These data indicate that both basal and stimulated production of EDRF are decreased in small arterioles in the striated muscle microcirculation at an established stage of genetic hypertension. These data suggest that a diminished EDRF response by arterioles may be in part responsible for the elevated microvascular reactivity observed in genetic hypertension.