Deficiency of Endogenous Angiotensin-(1-7) in the Nucleus Tractus Solitarii of (mREN2)27 Transgenic Rats May Account for Diminished Baroreceptor Reflex Function.

Abstract

17 Endogenous Ang-(1-7) facilitates and Ang II attenuates gain sensitivity of the baroreceptor reflex control of heart rate (HR) on the basis of injections of the Ang-(1-7) antagonist [D-Ala 7 ]-Ang-(1-7) or Ang II AT 1 antagonists into the solitary tract nucleus (nTS). In (mREN2)27 renin transgenic rats (TGR+), there is a 2 fold elevation of Ang II in the medulla oblongata while Ang-(1-7) levels are 50% that observed in normotensive SD rats. To determine the potential role of Ang-(1-7) in altered reflex function as a result of an imbalance of Ang peptides in the nTS, the baroreceptor reflex control of HR and cardiac chemoreceptor reflex were tested before and after bilateral injection of the [D-Ala 7 ]-Ang-(1-7) antagonist (144 pmol/120 nl) directly into the nTS of either SD or TGR+. HR and blood pressure (BP) responses to graded doses of phenylephrine were used to determine the slope of the relationship between changes in BP and changes in pulse interval for each animal (baroreceptor reflex sensitivity). TGR+ exhibited an impaired baroreflex compared with SD (0.9 ± 0.2 msec/mm Hg in SD, n = 8, versus 0.4 ±0.1 msec/mm Hg in TGR+, n = 6; p < 0.05). [D-Ala 7 ]-Ang-(1-7) attenuated the reflex (0.9 ± 0.2 msec/mm Hg before versus 0.4 ± 0.1 msec/mm Hg 10 minutes after antagonist, p < 0.05) in SD rats. There was no effect of [D-Ala 7 ]-Ang-(1-7) on the baroreflex in TGR+ (0.4 ± 0.1 msec/mm Hg before versus 0.4 ± 0.1 msec/mm Hg after) or on cardiac chemoreceptor activation by phenylbiguanide (10 μg/kg, iv bolus) in either strain [SD: -40 ± 7 mm Hg and -120 ± 36 beats/min before versus -36 ± 6 mm Hg and -108 ± 38 beats/min after; TGR+: -24 ± 5 mm Hg and -76 ± 31 beats/min before versus -25 ± 4 mm Hg and -106 ± 44 beats/min after]. The present findings indicate that endogenous Ang-(1-7) provides tonic input at novel, non-AT 1 , non-AT 2 receptors in nTS to facilitate reflex control of HR in normotensive but not hypertensive rats. Our studies further reveal that tonic effects of Ang-(1-7) in the nTS influence baro- but not cardiac chemoreceptor activation. (HL-38535, HL-51952, HL-07790)