Altered c-fos in Rostral Medulla and Spinal Cord of Spontaneously Hypertensive Rats

Jane Minson, Leonard Arnolda, Ida Llewellyn-Smith, Paul Pilowsky, John Chalmers. Hypertension. 1996; 27: 433-441 doi: 10.1161/01.HYP.27.3.433. Hypertension leads to elevated sympathetic nerve activity. We know that the RVM is important for tonic control of blood pressure and sympathetic nerve activity. The neurons located in the RVM are tonically active. C-fos is an early gene that is expressed in response to stimuli. In this particular study they wanted to investigate RVM neuronal activity in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) using c-fos. They also wanted to phenotype the cells by staining for serotonin and catecholamine. First they instrumented 16 to 18 week old WKY and SHR rats so they could record blood pressure and give an infusion of nitroprusside through femoral artery and vein, respectfully. Prior to the nitroprusside infusion, at 12 to 14 weeks CTB-gold was injected into the adrenal medulla and superior cervical ganglion. As for the controls there were two groups WKY and SHR rats that were just implanted with arterial and venous catheters but were not subject to surgical interventions. The infusion of nitroprusside leads to a fall in blood pressure in both groups along with reflex tachycardia. Obviously the saline did not cause a change in blood pressure and heart rate. The SHRs had an enhanced response to the nitroprusside infusion when compared to the WKYs. They then perfused the animal following the infusion and 60minute rest period. The prepared the tissue for immunostaining. Fos immunoreactivity was significantly higher in the nitroprusside group when compared to the saline WKYs. However, the SHRs had similar fos production between the saline and the nitroprusside group. But the SHR group still demonstrated higher fos immunoreactivity than the WKYs. They found that 50% of the TH positive neurons where positive for fos also in the nitroprusside group in the WKYs. As for the saline group, only a small amount was double labelled for fos and TH positive in WKYs. They also looked at serotonin neurons in the RVM. Fos immunoreactivity was not as prevalent in the serotonin population as it was in the TH population. They also looked at fos in the spinal cord. Both groups had a significant amount of fos in the T1-L1 segments s of the spinal cord. As for retrogradely labelled sympathetic preganglionic neurons, they found fos positive sympathetic preganglionic neurons projecting to the sympathoadrenal neurons in the SHRs. They were located in segments T7-T11 and accounted for 39% of all fos neurons in the SHRs. As for sympathetic preganglionic neurons projecting to the superior cervical ganglion there was a limited number found in the SHRs. In the WKYs, they found sympathetic preganglionic neurons projecting to the sympathoadrenal neurons in the t1-t13 region of the spinal cord. After nitroprusside 71% of the fos positive neurons were sympathetic preganglionic neurons projecting to the sympathoadrenal neurons in WKYs. As for the superior cervical ganglion, retrogradely labelled sympathetic preganglionic neurons were found in the T1-T5 region but now were immunoreactive for Fos after nitroprusside. The conclusion that was drawn from the studies at resting level in the SHRs, RVLM neuronal activity is elevated. This increased activity is driving the sympathoadrenal neurons mostly, and these neurons are contributing to the hypertension that is observed in the SHRs.-Mary