SUMMARY The distribution and density of nerves containing vasoactive intestinal polypeptide, substance P, and neuropeptide Y around the cerebral and peripheral blood vessels of stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) were studied using an indirect inununofluorescence technique. Neonatal sympathectomy of SHRSP with anti-nerve growth factor and guanethidine was also carried out to study the effect of sympathectomy on the distribution of these nerves. Vasoactive intestinal polypeptide nerve density was higher in the veins and superior mesenteric artery of SHRSP than of WKY and lower in the cerebral arteries of SHRSP than of WKY, but no difference was found in the muscular mesenteric arteries. Sympathectomy reduced the density of these nerves in all the peripheral vessels but had little effect on the cerebral arteries. Density of substance P nerves was similar between SHRSP and WKY in the peripheral vessels but higher in the cerebral arteries of WKY than of SHRSP. Sympathectomy reduced the density of these nerves in the peripheral vessels but increased the density in some cerebral arteries of SHRSP. Neuropeptide Y nerve density was higher in the peripheral blood vessels of SHRSP than of WKY, and no difference was found in the cerebral arteries. Sympathectomy almost completely removed these nerves in the peripheral vessels but had no effect on the cerebral arteries. We suggest that some of the differences in nerve density between SHRSP and WKY, especially those in the peripheral blood vessels, may be related to the development of hypertension in the SHRSP. around the blood vessels is generally unclear. Therefore, whether these nerves do play a role in the etiology of hypertension remains to be elucidated. For example, in Wistar rats, nerves containing dense substance P (SP) were found around superior mesenteric arteries.' A sensory function has been suggested for SP in the vascular nerves, 1 yet, neonatal treatment of spontaneously hypertensive rats (SHR) with capsaicin, which presumably depletes neuronal SP, also prevented hypertension development in these rats, 2 suggesting SP may have other functions besides a sensory function. In our recent study on the effect of sympathectomy on hypertension development and vessel wall morphology, 3 we found that despite the destruction of sympathetic nerves with our procedure, other nerve types were still present.The primary aim in our present study was to locate and identify various peptide-containing nerves from the cerebral and peripheral blood vessels of stroke-prone SHR (SHRSP) and Wistar-Kyoto rats (WKY). Our intent was to relate the distribution of these nerves to the known action of the peptides so that we could gain some understanding concerning the possible involvement of these nerves in the development of hypertension.Materials and Methods SHRSP and WKY were obtained from rat colonies currently maintained at the McMaster University Animal Quarters. Male rats, 6 months of age or older, were used. Blood vessels were...