Pressor and Reflex Sensitivity Is Altered in Spontaneously Hypertensive Rats Treated With Angiotensin-(1-7)

Abstract

Abstract We have suggested that angiotensin-(1-7) [Ang-(1-7)] may oppose the pressor activity of angiotensin II (Ang II). This hypothesis was supported by the fact that long-term intravenous infusion of Ang-(1-7) transiently lowers blood pressure in spontaneously hypertensive rats (SHR). We now investigated whether the pressor sensitivity to bolus injections of either phenylephrine (PE) or Ang II was altered on day 12 of an Ang-(1-7) infusion when blood pressure in the SHR had returned to hypertensive levels. SHR (n=10) and WKY rats (n=8) were given Ang-(1-7) intravenously via osmotic minipumps at a dose of 24 μg/kg per hour for 2 weeks. On day 12 of the infusion, mean arterial pressure and heart rate in halothane-anesthetized rats were similar in Ang-(1-7)–treated SHR (142±6 mm Hg; 388±9 beats per minute) and those infused with vehicle (146±5 mm Hg; 392±13 beats per minute). Pressor responsiveness to PE in Ang-(1-7)–treated SHR was 22% less at a dose of 10 μg, while pressor responses to Ang II decreased by 20% and 25% at doses of 0.05 and 0.1 μg, respectively, compared with the vehicle-treated SHR ( P <.05). There were no effects of the Ang-(1-7) infusion on pressor responses to Ang II or PE in WKY rats. In the SHR infused with Ang-(1-7), there was a 35% improvement in sensitivity of the reflex control of heart rate to levels not different from those in the untreated WKY rats (slope of the change in pulse interval versus the change in pressure increased from 0.34±0.03 to 0.46±0.01 ms/mm Hg). These data suggest that Ang-(1-7) may selectively activate antihypertensive mechanisms at the level of the vascular wall or the baroreflex.