Exercise training rescues the electrical activity of liver-projecting DMNV neurones in response to oxytocin in spontaneously hypertensive rats.

A neural circuit between the paraventricular nucleus of the hypothalamus (PVN) and the dorsal motor nucleus of the vagus (DMNV) constitutes part of an important parasympathetic autonomic pathway that controls hepatic glucose production. Intracerebroventricular injection of insulin activates oxytocinergic neurones in the PVN and elicits the release of oxytocin into the circulation, which plays an important role in the metabolism of glucose. Moreover, the central action of insulin can reduce the concentration of glucose in blood taken from the hepatic vein of Wistar rats via activation of vagal efferent nerves to the liver. This mechanism is impaired in sedentary spontaneously hypertensive rats (SHR). Because aerobic exercise increases vagal tone, partly mediated by increasing the oxytocinergic connections between the PVN and DMNV, we hypothesised that oxytocin (OT) might alter the excitability of liver-projecting DMNV neurones. Thus, we investigated the effects of OT on electrical properties of the liver-projecting DMNV neurones from Wistar, SHR subjected to 4 weeks of exercise training, as well sedentary controls, using whole cell patch-clamping. The results show that OT increased the resting membrane potential of DMNV neurones in Wistar rats, as well as the firing frequency of these cells, but not in sedentary SHR. However, in SHR subjected to 4 weeks of exercise training, the effects of OT on liver-projecting DMNV neurones of were similar to those seen in Wistar rats. These findings show that OT elicits similar changes in the electrophysiological properties of liver-projecting DMNV neurones of Wistar and exercise-trained but not sedentary SHR. These results indicate that exercise training can restore the sensitivity of liver-projecting DMNV neurones of exercise-trained SHR to OT.

Temporal profile and mechanisms of the prompt sympathoexcitation following coronary ligation in Wistar rats.

Our aim was to assess the timing and mechanisms of the sympathoexcitation that occurs immediately after coronary ligation. We recorded thoracic sympathetic (tSNA) and phrenic activities, heart rate (HR) and perfusion pressure in Wistar rats subjected to either ligation of the left anterior descending coronary artery (LAD) or Sham operated in the working heart-brainstem preparation. Thirty minutes after LAD ligation, tSNA had increased (basal: 2.5±0.2 µV, 30 min: 3.5±0.3 µV), being even higher at 60 min (5.2±0.5 µV, P<0.01); while no change was observed in Sham animals. HR increased significantly 45 min after LAD (P<0.01). Sixty minutes after LAD ligation, there was: (i) an augmented peripheral chemoreflex - greater sympathoexcitatory response (50, 45 and 27% of increase to 25, 50 and 75 µL injections of NaCN 0.03%, respectively, when compared to Sham, P<0.01); (ii) an elevated pressor response (32±1 versus 23±1 mmHg in Sham, P<0.01) and a reduced baroreflex sympathetic gain (1.3±0.1 versus Sham 2.0±0.1%.mmHg-1, P<0.01) to phenylephrine injection; (iii) an elevated cardiac sympathetic tone (ΔHR after atenolol: -108±8 versus -82±7 bpm in Sham, P<0.05). In contrast, no changes were observed in cardiac vagal tone and bradycardic response to both baroreflex and chemoreflex between LAD and Sham groups. The immediate sympathoexcitatory response in LAD rats was dependent on an excitatory spinal sympathetic cardiocardiac reflex, whereas at 3 h an angiotensin II type 1 receptor mechanism was essential since Losartan curbed the response by 34% relative to LAD rats administered saline (P<0.05). A spinal reflex appears key to the immediate sympathoexcitatory response after coronary ligation. Therefore, the sympathoexcitatory response seems to be maintained by an angiotensinergic mechanism and concomitant augmentation of sympathoexcitatory reflexes.