SUMMARY. Autonomic innervation in the cerebral arterial walls of adult male spontaneously hypertensive rats and of normotensive Wistar-Kyoto rats was studied. When examined by fluorescence microscopy, dense catecholamine fluorescence was observed in anterior cerebral and middle cerebral arteries of both Wistar-Kyoto and spontaneously hypertensive rats. However, vertebral and basilar arteries and small pial arteries of Wistar-Kyoto rats received extremely sparse or no catecholamine fluorescence, whereas, in the respective regions of spontaneously hypertensive rats, catecholamine fluorescence was found to be significantly elevated. The endogenous norepinephrine content was also higher in cerebral arteries of spontaneously hypertensive than of Wistar-Kyoto rats. When examined ultrastructurally (potassium permanganate fixation), the incidence of granular vesicle-containing nerves, indicative of sympathetic nerves, was found to be significantly elevated in all cerebral arteries of spontaneously hypertensive rats examined. In contrast, the agranular vesicle-containing nerve, indicative of nonsympathetic nerves, with close synaptic cleft distance (<2 /im) was found to decrease or remain unchanged in the cerebral arteries of spontaneously hypertensive rats. These results suggest that cerebral sympathetic vasoconstriction may become more prominent than nonsympathetic vasodilation in spontaneously hypertensive rats. This finding lends further credence to the previous in vivo findings that cerebral sympathetic vasoconstrictor nerves become more functional and exhibit a protective effect against brain lesions during hypertension. The potential roles of neurogenic components involved in cerebral blood flow autoregulation are also discussed. (Circ Res 55: 392-403, 1984)

SUMMARY The ultrastructural distribution of the autonomic nerves of brain arteries was investigated in renal (one-kidney, one clip) hypertensive and normotensive Wistar-Kyoto rats. Sympathetic and nonsympathetic nerve terminals were found only in the adventitial layer of brain arteries of renal hypertensive and normotensive rats. In both normotensive and renal hypertensive rats the total nerve endings were dense in anterior cerebral artery, moderately dense in middle cerebral artery, and sparse in basilar artery. In normotensive rats, nonsympathetic nerves outnumbered sympathetic nerves in anterior cerebral, middle cerebral, and basilar arteries. In renal hypertensive rats these two types of nerve terminals in close apposition to smooth muscle decreased in anterior cerebral and basilar arteries, while those in middle cerebral arteries remained unchanged. These results suggest that the potential neurogenic control of cerebral blood vessels as well as the trophic effect of sympathetic nerves on brain blood vessels may decrease in renal hypertensive rats. As this finding contrasts with that in spontaneously hypertensive rats, the pattern of innervation in brain arteries may differ in different types of hypertension. (Hypertension 7: 514-518, 1985) KEY Tissue concentrations of norepinephrine are reported to be decreased in mesenteric artery and heart in renal hypertensive animals.10 " On the other hand, the density of sympathetic innervation has been shown to increase in brain arteries of the spontaneously hypertensive rats (SHR).5 -l2 Furthermore, autoregulation of lower and higher limits of cerebral blood flow has been reported to change in hypertensive animals. 13 "" These results suggest that autonomic nerves undergo some changes when the animal becomes hypertensive. Alterations in the pattern of autonomic nerves may be different depending on the type of hypertensive model. In this study, we therefore examined and compared the ultrastructural distribution of sympathetic and nonsympathetic nerve terminals and their relationship to smooth muscle cells in the cerebral arterial walls of renal (one-kidney, one clip) hypertensive rats (RHR) and normotensive rats (NR). MethodsThe experiments were performed on normotensive male Wistar-Kyoto rats. Chronic renal hypertension was induced in 7-week-old rats by placing a silver clip (internal diameter, 0.25 mm) over the left renal artery through a left lumbar incision and followed 1 week later by contralateral nephrectomy. The control animals were sham-operated. The left kidney was exposed after a lumbar incision and was manipulated without compressing the artery. The operating time was approximately the same as that of the procedure for artery clipping. One week later the contralateral kidney was also exposed but not removed. All of the procedures were accomplished with the rats under sodium pentobarbital (Nembutal, 50 mg/ml). The systol-