The sinoaortic denervated (SAD) rat has mild hypertension and labile arterial pressure associated with body movements and haselevated plasma vasopressin. Recent investigations revealed that tyrosine hydroxylase (TH) activity and dopamine (DA) concentration were reduced in the caudate nucleus of SAD rats and that TH activity was also reduced in substantia nigra and supraoptic nucleus (SON). Since the nigrostriatal system is a major site of somatomotor neural integration and since centrally active DA agonists have a blood pressure lowering effect in some forms of hypertension, the hypothesis will be tested that reduced DA metabolism in the nigrostriatum causes the characteristic body movement- related pressure lability of SAD rats and contributes to their mild hypertension. Microinjections of DA agonists will be made into the nigrostriatum of freely moving SAD and sham-operated control rats whose arterial pressure and heart rate are being continuously recorded. An on-line DEC computer will generate frequency-interval histograms, mean and standard deviation values of pressure and heart rate. Hemodynamic effects of lesioning nigrostriatal region of normal rats will also be evaluated. Another hypothesis to be tested is that reduced synthesis and release of catecholamines in the hypothalamus disinhibits vasopressin secretion in SAD rats. In vivo and in vitro TH activity, release and turnover of catecholamines in SON and paraventricular nucleus will be measured. The time of onset and duration of biochemical changes in both nigrostriatal and hypothalamic regions will be studied. Onset of changes in caudate also will be evaluated by in vivo voltammetry which, in pilot studies, indicated DA was released by sinoaortic denervation. All biochemical assays will be sensitive, specific and radioisotopic. Finally immunohistofluorescent probes will be used to look for evidence of projections between brain stem areas associated with cardiovascular regulation and the substantia nigra.
| Alexander, N; Morris, M (1988) Effects of chronic sinoaortic denervation on central vasopressin and catecholamine systems. Am J Physiol 255:R768-73 |
| Alexander, N; Melmed, S; Morris, M (1987) Suppressed serum prolactin in sinoaortic-denervated rats. Am J Physiol 252:R290-3 |
