Role of endogenous nitric oxide in the nucleus tratus solitarii on baroreflex control of heart rate in spontaneously hypertensive rats.

Abstract

Toinvestigate the modulatory effect of endogenous nitric oxide (NO) in the nucleus tractus solitarii (NTS) on the baroreceptor reflex control of heart rate in conscious spontaneously hypertensive (SHR) and normotensive (WKY) rats. Male age- and weight-matched SHR and WKY chronically instrumented with cannulas in the NTS, artery and vein were used. Basal pressure (AP), heart rate (HR) and reflex HR responses during loading/unloading of baroreceptors (phenylephrine/sodium nitroprusside, iv) were recorded during vehicle (3 nl/min) NG-monomethyl-L-arginine (L-NMMA) and L-arginine (L-Arg) infusions into the NTS. Constitutive NO synthase (NOS) activity was inferred by 3H-citrulline formation in the dorsal brain stem of other SHR and WKY groups. In SHR a small dose of L-NMMA (30 ng/kg/min) restricted to the NTS did not change AP and HR (185+/-4 mmHg, 373+/-12 beats/min, respectively), but decreased the HR range (57+/-7 beats/min, a 34% reduction, P< 0.05) without changing further the impaired gain of baroreceptor reflex control of HR. In the WKY group similar results (significant 32% reduction in HR range, gain unchanged) were only attained with a dose 10 times higher (L-NMMA(NTS) = 300 ng/kg/min), no effect being observed with the small dose (HR range = 163+/-12 beats/min). In SHR, L-Arg(NTS) (900 ng/kg/min) did not improve baroreflex control of HR, but restored the depression of HR range when given after L-NMMA(NTS). Basal NOS activity in the dorsal brain stem was reduced in SHR (P < 0.05) when compared to WKY group. NO modulates, at the NTS level, the baroreceptor reflex control of HR in both SHR and WKY not by altering the gain, but by increasing HR range during afferent stimulation. In SHR the depressed NO modulation is in accordance with the smaller NOS activity in the dorsal brain stem.