Chronotropic response to cardiac sympathetic nerve stimulation in spontaneously hypertensive rats

In Sprague-Dawley rats, we attempted to develop an experimental model to stimulate the cardiac sympathetic nerve. After transverse thoracotomy under anesthesia, a miniature, bipolar electrode was placed on the right ansa subclavia and it was stimulated electrically. The nerve stimulation at 2, 4, and 8.3 Hz (2 ms in duration, 5 V) increased heart rate by 21.2 +/- 4.19, 34.2 +/- 5.33, and 47.8 +/- 9.25 beats min-1, respectively (p < 0.05). Tetrodotoxin abolished the chronotropic response evoked by nerve stimulation at 4 Hz (p < 0.05). The beta-adrenergic receptor antagonist propranolol abolished the chronotropic response (p < 0.005). These results indicate that the cardiac sympathetic nerve secretes norepinephrine as a neurotransmitter and that the electrical stimuli did not directly stimulate the cardiac tissues. Thus, our preparation is appropriate for stimulation of the cardiac sympathetic nerve. We then determined the extent of the positive chronotropic responses evoked by electrical stimulations of the cardiac sympathetic nerve in spontaneously hypertensive rats (SHR) and compared the results with those in Wistar-Kyoto rats (WKY). At 5-7 weeks of age, the extent of positive chronotropic responses at 2, 4, and 8.3 Hz in SHR was 16.1 +/- 3.5, 25.2 +/- 3.8, 32.2 +/- 4.3 beats.min-1, respectively, and the extent was not different from results in WKY at the same age. At 15-17 weeks of age, the positive chronotropic responses at 2, 4, and 8.3 Hz in SHR were 6.6 +/- 1.6, 15.7 +/- 2.8, and 22.3 +/- 4.0 beats.min-1, respectively, and were significantly less than those in WKY at the same age (p < 0.05). Also, responses in SHR at 15-17 weeks were significantly less than in SHR at 5-7 weeks (p < 0.05). The same degree of positive chronotropic response evoked by peripheral cardiac sympathetic nerve stimulation in both SHR and WKY at 5-7 weeks during the developmental phase of hypertension suggests that the overactivity of the sympathetic nerve known to occur during this phase in SHR may not be produced by the postganglionic nerve fiber per se, but rather by increased activity in the central nervous system. The reduced positive chronotropic response as hypertension is established may indicate that it is developed in the course of a high blood pressure state, but it is not the inherent nature of hypertension.