Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, C4
Peripheral Cardiac Sympathetic dysfunction in the pre-hypertensive Spontaneously Hypertensive Rat
N. Herring1, S. Manou-Stathopoulou1, D. Li1, D. J. Paterson1
1. Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
Increased peripheral cardiac sympathetic activity has been identified in the spontaneously hypertensive rat (SHR) compared to age matched normotensive Wistar Kyoto (WKY) controls. However, it is not clear whether this sympathetic hyperactivity precedes the development of the hypertensive phenotype. We therefore compared peripheral cardiac sympathetic responsiveness in the SHR to the WKY at 3-6 week of age. Ventricular weight, body weight ratios and in-vivo measurements of mean arterial pressure via a 3F catheter inserted into the carotid artery under general anaesthesia (1-3% Isoflurane), demonstrated that SHRs (n=8) were without left ventricular hypertrophy and were normotensive at this age compared to WKYs (n=7). In an isolated organ bath double atrial preparation with intact right stellate ganglion (at 37±0.5°C), there was a significantly increased (unpaired Students t-test, p<0.05) heart rate response to right stellate stimulation at 5 and 7Hz (15V, 1msec) in SHRs (n=9) compared to WKYs (n=7). This was also associated with a significantly greater sensitivity to bath applied noradrenaline (100nM to 2μM) in SHRs (n=8) compared to WKYs (n=9). After loading isolated atria with [3H]-noradrenaline (0.185MBq), there was a significantly greater release of [3H]-noradrenaline to field stimulation (5Hz, 15V, 1msec) in the SHR compared to the WKY (n=7 for both groups). Moreover, the presynaptic α2 receptor antagonist yohimbine (1μM), did not alter the [3H]-noradrenaline release between the two groups. In isolated cultured neurons from stellate ganglia, the magnitude of the calcium transient in response to depolarization from high extracellular potassium was significantly larger in SHRs (122.1±16.7%, n=10) compared to WKYs (91.7±13.1%, n=8). These results show that the enhanced transient is also associated with increased cardiac noradrenaline release which translates into a greater heart rate responsiveness in young SHRs compared to WKYs. The increased release of noradrenaline is likely due to a greater neuronal calcium transient rather than impaired presynaptic α2 receptor mediated autoinhibition. In conclusion, the autonomic phenotype in pre-hypertensive rats occurs both pre and post synaptically, and may represent an early marker in the development of hypertension itself.
Where applicable, experiments conform with Society ethical requirements