Aim: We have demonstrated hypertension mediated by failure to upregulate PVN Gαi2 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 Gαi2 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 Gαi2 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. Gαi2 treated rats (IV 3M NaCl ΔHR [bpm]; SCR -79±15 vs. Gαi2 -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. Gαi2 149±3). In SCR rats, MAP returned to baseline by 100 min whereas Gαi2 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. Gαi2 -22±8) or peak MAP changes (ICV 1M NaCl ΔMAP [mmHg] 16±3 mmHg vs. Gαi2 9±3). In SCR rats, MAP returned to baseline by 50 min whereas Gαi2 rats remained elevated for 90 min. The 24h Gαi2 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, Gαi2 HR=307 bpm, P<0.05).
Conclusion: Downregulation of Gαi2 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 Gαi2 proteins in the baroreflex control of HR at elevated blood pressures—a factor that may contribute to elevated MAP in neurogenic models of hypertension.