Altered cardiovascular responses to purinergic A2 stimulation in the nucleus tractus solitarius of spontaneously hypertensive rats.

Abstract

To investigate the cardiovascular effects of adenosine A2 receptor stimulation in the nucleus tractus solitarius and whether these effects are altered in hypertension. Ten- or 11-week-old spontaneously hypertensive rats (SHR) or Wistar-Kyoto (WKY) rats were anaesthetized with urethane. Adenosine (100 ng) or adenosine A2 agonist (2-octynyladenosine, 5 ng) were micro-injected (50 nl) into the nucleus tractus solitarius. Blood pressure and heart rate were measured from a femoral artery. Sympathetic nerve activity was recorded from the abdominal splanchnic nerve. Blood pressure, heart rate and sympathetic nerve activity were consistently decreased after the micro-injection of adenosine into normotensive rats. Changes from the baseline in blood pressure, heart rate and sympathetic nerve activity were significantly smaller in SHR than in WKY rats (blood pressure: SHR -5.6 +/- 2.1% versus WKY rats -20.0 +/- 2.1%; heart rate: SHR -5.4 +/- 0.88% versus WKY rats -9.2 +/- 2.3%; sympathetic nerve activity: SHR -5.5 +/- 1.1% versus WKY rats -21 +/- 2.8%). Micro-injection of an A2 agonist into the nucleus tractus solitarius also decreased blood pressure and heart rate, and those responses were not inhibited by pretreatment with an adenosine A1-specific antagonist. The response induced by micro-injection of A2 agonist into the nucleus tractus solitarius was significantly smaller in SHR than in WKY rats, whereas the changes in heart rate did not differ statistically (blood pressure: -23.4 +/- 4.7% versus -10.8 +/- 2.1%; heart rate: -12.1 +/- 1.2% versus -13.6 +/- 2.1%). The present results suggest that stimulation of adenosine A2 receptors in the nucleus tractus solitarius decreases both blood pressure and inhibitory sympathetic nerve activity and that those inhibitory responses to adenosine in the nucleus tractus solitarius are deranged in SHR.