Abstract 293: Brain Gai2 Proteins Mediate Acute Neural Blood Pressure Responses to Centrally and Peripherally Administered NaCl

Abstract

Aim: We have demonstrated hypertension mediated by failure to upregulate PVN Gαi 2 proteins in rats fed a chronic high salt diet, but the role of this mechanism is unknown in acute settings. We examined the effect of central Gαi 2 proteins in the neural control of blood pressure in response to an acute physiological (IV and ICV) and pharmacological challenge. Methods: Twenty-four hour (24-h) ICV Gαi 2 or SCR oligodeoxynucleotide (ODN; 25μg/5μl)-pretreated conscious Sprague-Dawley rats were continuously monitored for changes in HR and MAP in response to peripherally-administered NaCl (3M IV bolus; 0.14 ml/100g) or centrally-administered NaCl (1M ICV; 5μL)(N=4/gp). To determine the cardiac baroreflex MAP was slowly raised to ~175 mmHg using phenylephrine and lowered to ~50 mmHg using sodium nitroprusside in separate group of pre-treated rats (N=8/gp). Results: In response to IV sodium, peak changes in HR were significantly greater in SCR vs. Gαi 2 treated rats (IV 3M NaCl ΔHR [bpm]; SCR -79±15 vs . Gαi 2 -59±12, P<0.05), but no difference was observed in peak changes in MAP (IV 3M NaCl ΔMAP [mmHg] SCR 147±4 mmHg vs . Gαi 2 149±3). In SCR rats, MAP returned to baseline by 100 min whereas Gαi 2 rats remained significantly elevated for 120 min (P<0.05). In response to ICV sodium, we observed no difference between groups in peak HR changes (ICV 1M NaCl ΔHR [bpm] -23±8 bpm vs . Gαi 2 -22±8) or peak MAP changes (ICV 1M NaCl ΔMAP [mmHg] 16±3 mmHg vs . Gαi 2 9±3). In SCR rats, MAP returned to baseline by 50 min whereas Gαi 2 rats remained elevated for 90 min. The 24h Gαi 2 ODN pretreatment significantly altered the high-, but not low-pressure gain of the baroreflex in response to pharmacological challenge (MAP=180 mmHg, SCR HR=270 bpm, Gαi 2 HR=307 bpm, P<0.05). Conclusion: Downregulation of Gαi 2 proteins resulted in altered cardiac baroreflex function by impairing reflex decreases in HR and mediating significantly prolonged elevated MAP in response to peripherally administered sodium. This highlights a previously undiscovered role of brain Gαi 2 proteins in the baroreflex control of HR at elevated blood pressures—a factor that may contribute to elevated MAP in neurogenic models of hypertension.