Chronic cerebroventricular infusion of hypertonic sodium chloride in rats reduces hypothalamic sympatho-inhibition and elevates blood pressure.

Abstract

SUMMARY. To determine whether or not salt loading restricted to the brain would elevate blood pressure, chronically implanted osmotic minipumps were used to infuse hypertonic sodium chloride solutions made in artificial cerebrospinal fluid into a jugular vein intravenously or the third cerebral ventricle, intracerebroventricularly, for 11 days in awake rats. During intracerebroventricular infusion of hypertonic sodium chloride, tail-cuff systolic pressures began to rise on day 4 and were significantly elevated by day 9. In contrast, infusions of either artificial cerebrospinal fluid alone, intracerebroventricularly, or hypertonic sodium chloride, intravenously, were ineffective. Confirming the blood pressure elevation thereby detected, systolic and mean pressures recorded directly from indwelling aortic catheters after the same rats had been anesthetized with urethane on day 11, were also significantly higher following intracerebroventricular infusion of hypertonic sodium chloride than after infusion of artificial cerebrospinal fluid alone. Magnitude of depressor and sympatho-inhibitory responses elicited by graded electrical stimulation of the anterior hypothalamus invariably increased with the current strength used for stimulation. At all current strengths used for hypothalmic stimulation, depressor responses as well as attendant decreases in sympathetic neural firing, were smaller in rats that had been infused intracerebroventricularly with hypertonic sodium chloride than in any of the controls. Inhibition seemed specific for the anterior hypothalamus because pressor responses to stimulation of the ventromedial hypothalamus were the same whether or not the intracerebroventricular infusion contained hypertonic sodium chloride. An explanation based on diminished cardiovascular sensitivity also appeared unlikely, since depressor responses to intravenously injected histamine were almost equal in both groups. Our results are compatible with the interpretation that hypertonic sodium chloride infused chronically into the 3rd ventricle acts by reducing anterior hypothalamic inhibition of sympathetic vasomotor tone, and that this, in turn, then elevates blood pressure. (Circ Res 54:566-575, 1984) ALTHOUGH the hypertensive effects of excessive salt intake in rats have often been attributed to peripheral sympathetic or renal pressor mechanisms, recent evidence suggests that a centrally induced sympathetic overactivity may also be involved. Together with the blood pressure elevation produced by deoxycorticosterone acetate (DOCA)-salt pretreatment, norepinephrine turnover decreases in the hypothalamus and brainstem (Nakamura et al., 1971; van Ameringen et al., 1977). In Dahl salt-sensitive rats, dietary salt loading enhances pressor responsiveness to intracerebroventricular (icv) injections of hypertonic saline solution (Ikeda et al., 1978) and to electrical stimulation of the ventromedial hypothalamus (Bunag et al., 1983). Furthermore, the resulting hypertension is greatly attenuated after either chemical destructio...

Effects of chronic intraventricular sodium on blood pressure and fluid balance.

“…Our results confirm the findings of a few previous studies. Miyajima and Bunag 17 showed that third ventricular infusion of 0.8 M NaCl at the same infusion rate for 11 days elevated blood pressure in rats. Katahira et al 21 also observed that chronic administration of 1.5 M NaCl into the lateral ventricle of rats caused a moderate increase in blood pressure.…”

“…14 -16 Although the central effects of hypertonic NaCI are well documented in acute experiments, there are few chronic studies. Miyajima and Bunag 17 reported that intracerebroventricular infusion of hypertonic NaCI for 11 days caused mild hypertension and reduced depressor response to anterior hypothalamic stimulation in rats. They also observed that impairment of the baroreceptor reflex preceded the rise in blood pressure.…”

Estrogen Depletion Increases Blood Pressure and Hypothalamic Norepinephrine in Middle-Aged Spontaneously Hypertensive Rats

“…12,13 These and other results indicate that dietary NaCl loading increases blood pressure in male SHR by reducing norepinephrine release in AHN, thus removing an important sympatho-inhibitory mechanism that normally modulates arterial pressure. [25][26][27][28][29] Other studies indicate that a high NaCl diet elevates plasma sodium, which in turn activates osmo-receptive neurons in the circumventricular hypothalamic nuclei. 30 -32 The activation of these neurons thereby suppresses norepinephrine release from axon terminals in AHN, probably via an indirect pathway that includes an inhibitory neuromodulator.…”

Handling 22 NaCl by the Blood-Brain Barrier and Kidney

“…The reason for a less rapid increase of heart rate in DS rats remains unclear. Miyajima and Bunag 32,33 suggested that chronic infusion of hypertonic sodium into the third ventricle of Sprague-Dawley rats reduces hypothalamic inhibition of sympathetic vasomotor tone and impairs the baroreflex, which then elevates BP. NaCl uptake by the brain of DS rats appeared to result from increased permeability of the BBB to sodium, whereas renal 22 Na retention resulted from impaired excretion of 22 Na.…”