Neurogenic Hypertension in the Rat

Abstract

Several techniques of radical denervation of the sino-aortic depressor areas were tried in order to produce a permanent neurogenic hypertension in the rat. The aortic depressor fibers were interrupted at the neck level by resecting the nerves which usually exhibit baroreceptor activity, namely, isolated aortic nerve, sympathetic, and laryngeal nerves. The carotid sinus was denervated by stripping the carotid bifurcation and painting with phenol. When the carotid bifurcation was resected bilaterally, in a one-stage operation, all rats showed symptoms of cerebral ischemia, dying shortly thereafter. Isolated denervation of the aortic baroreceptors was followed by a transitory hypertension. No changes in preasure were observed when only the carotid sinuses were denervated. A few rats in which the usual baroreceptor pathways were interrupted, except the superior laryngeal nerve, developed chronic hypertension. Yet, to obtain consistently permanent hypertension it was necessary to include in the denervation every baroreceptor route. A simple one-stage operation for complete sino-aortic baroreceptor denervation is described. This procedure was used in 140 rats that were then studied for periods up to one year. All the operated animals presented some degree of hypertension. Blood pressure measurements made during the first week showed even then that the rats were hypertensive. This observation suggests that in the rat no latent period for the appearance of neurogenic hypertension is present. Hypertension was permanent in 75% of the rats observed up to one year; blood pressure returned to normal values in the remaining 25%, usually after the third month. Extirpation of the adrenal medulla had no effect on the evolution of the hypertension in the denervated rats. Blood pressure was measured repeatedly in unanesthetized rats by tail plethysmography. Pressure values determined by this method, though 10 to 20 mm Hg lower, approximated the mean arterial pressure recorded directly from the femoral artery in normotensive and hypertensive rats. The hypertension in denervated rats included an increase of systolic as well as diastolic pressure. The heart rates of quiet hypertensive rats were within the normal range and, in general, no close correlation was observed between increases in blood pressure and elevations in heart rate. Normal rats have marked fluctuations in both pressure and heart rate when walking or when stimulated; these fluctuations were much greater in the neurogenic hypertensive animals. Moreover, the hypertensive rats showed large oscillations of blood pressure synchronous with respiratory movements particularly when the latter were slower and deeper than normal. The rats seemed to tolerate both the denervation and the hypertension very well. Histological examination of tissues from hypertensive rats showed myocardial hypertrophy and a thickening of the basement membrane of the glomerular capsule. The severity of the latter abnormality was closely associated with the duration of the hypertension.