Contribution of the sympathetic nervous system to the hypertensive effect of a high sodium diet in stroke-prone spontaneously hypertensive rats.

In stroke-prone spontaneously hypertensive rats (SHRSP) plasma norepinephrine levels and vascular reactivity to norepinephrine are increased and intravascular volume is reduced during the developmental phase of hypertension. Since the accelerated rise in blood pressure following sodium-loading in SHRSP cannot be attributed to the volume-retaining properties of sodium, the effects of an increased dietary intake of sodium on biochemical parameters of sympathetic vascular tone were investigated. The following results were obtained. First, the increased reactivity of vascular smooth muscle was further augmented in sodium-treated SHRSP; the degree of supersensitivity was positively correlated to the plasma sodium concentration. After blockade of the neuronal uptake by 30 microM cocaine, no difference in vascular reactivity to norepinephrine was detected between SHRSP on a normal and SHRSP on a high-sodium diet. Second, the inactivation of norepinephrine by the neuronal uptake was impaired in rats on a high-sodium diet, the impairment being more pronounced in SHRSP than in Wistar-Kyoto (WKY) rats. This decreased inactivation could be expected to cause higher concentrations of the neurotransmitter at the receptor site if the transmitter release from the nerve ending remains constant. Third, the release of norepinephrine and epinephrine into the plasma was increased in sodium-loaded SHRSP but not in sodium-loaded WKY. Cold exposure exaggerates these differences between normotensive and hypertensive rats. These findings suggest that a high-sodium intake modifies the transmission of sympathetic impulses at the level of the nerve terminal in both WKY and SHRSP. In the normotensive rats, moderate impairment of norepinephrine inactivation, however, was balanced by an appropriate reduction in central sympathetic discharge following sodium-loading. In the hypertensive rats, the peripheral disturbance in norepinephrine inactivation due to sodium-loading was obviously not balanced by an adequate withdrawal of central sympathetic discharge. The resultant hemodynamic change was a further increase in the sympathetically mediated vasoconstriction, which is regarded as at least one of the main mechanisms of the sodium-dependent acceleration of hypertension in SHRSP.