Developing renal innervation in the spontaneously hypertensive rat: evidence for a role of the sympathetic nervous system in renal damage

The spontaneously hypertensive rat (SHR) exhibits increased renal sympathetic nerve activity and neurotransmitter levels compared with the control Wistar-Kyoto rat (WKY). These renal nerve abnormalities have been implicated as the cause of hypertension in the SHR. The aims of the present study were to characterize the ontogeny of renal sympathetic innervation in SHR in order to determine any functional implications. Glyoxylic acid histofluorescent and radio-enzymatic norepinephrine assays demonstrated an accelerated development of renal innervation in newborn and 1-, 2-, 3- and 6-week-old SHR compared with WKY. Sympathetic nervous system function was blocked in developing male SHR by treating pups from days 0 to 14 with: (1) guanethidine, (2) combined alpha- and beta-receptor antagonists (prazosin and timolol), or (3) vehicle (5% sucrose). Blood pressure (mean), renal function (plasma creatinine) and histologic renal damage were assessed at 42 weeks of age. Although the blood pressure of the drug-treated rats remained elevated, renal damage was reduced and renal function was improved compared with control (sucrose-treated) SHR. The data demonstrate that the SHR kidney develops a precocious sympathetic innervation and that inhibition of the development of sympathetic function ameliorates renal damage independently of systemic hypertension.