Li-Chik Lee

Central attenuation of aortic baroreceptor reflex in prehypertensive DOCA-salt-loaded rats.

To determine whether the arterial baroreceptor reflex can act to oppose the development of hypertension, deoxycorticosterone acetate (DOCA)-salt hypertension was produced in sinoaortlcdenervated and sham-operated rats. Systolic blood pressure measured by tail cuff started to increase in both sinoaortic-denervated and sham-operated rats 7 days after DOCA treatment, and the hypertension developed identically in both denervated and sham-operated rats. These findings suggest that the baroreceptor reflex cannot act against the development of hypertension. To determine whether the baroreceptor reflex is attenuated before the development of hypertension, bradycardic and sympathoinhibitory responses to i.v. injections of norepinephrine were examined. Bradycardic and sympathoinhibitory responses were significantly smaller in DOCA-salt-treated rats in both prehypertensive (5th day after DOCA-salt treatment) and hypertensive stages (21st day after treatment). In urethane-anesthetized DOCA-loaded and control rats on the 5th day after treatment, aortic depressor nerve stimulation elicited frequency-dependent depressor and bradycardic responses accompanied by inhibition of sympathetic nerve activity in both DOCA-loaded and control rats. However, those responses were significantly smaller in DOCA-loaded rats than in control rats. These results suggest that the central component of the baroreceptor reflex mediated by the aortic depressor nerve is impaired before hypertension develops and that this impairment may contribute to the development of hypertension in DOCA-salt-treated rats.

Attenuated cardiovascular and sympathetic nerve responses to aortic nerve stimulation in DOCA-salt hypertensive rats

In order to verify, whether baroreflex sensitivity is changed centrally in DOCA-salt hypertension, the left aortic depressor nerve (ADN) was electrically stimulated in DOCA-salt hypertensive rats. After 3 weeks, tail-cuff systolic pressure was significantly higher in DOCA-salt treated rats than in untreated rats (169 +/- 4 versus 130 +/- 4 mmHg, respectively; P less than 0.001). After cutting both ADN and the carotid sinus nerves, the central cut end of the left ADN was electrically stimulated and frequency dependent depressor, bradycardic and sympatho-inhibitory responses were elicited in both control and DOCA-salt hypertensive rats. However, these responses were significantly smaller in DOCA-salt hypertensive rats than in normotensive controls. Bradycardic and sympatho-inhibitory responses to i.v. injection of norepinephrine were also blunted in DOCA-salt hypertensive rats. These findings suggest that baroreflexes were centrally attenuated in DOCA-salt hypertensive rats and possibly contribute to overall baroreflex attenuation.

Salt increases blood pressure with biphasic changes in hypothalamic responsiveness in rats

Tail-cuff systolic pressures became elevated in male Wistar rats fed chow containing 8% NaCl for 4 weeks. After 4 weeks of salt loading, pressor and sympathetic responses to ventromedial hypothalamic stimulation were larger in salt-loaded rats. When similar experiments were done following sinoaortic denervation, all of the effects previously induced by dietary salt loading persisted. By contrast, after only 1 week of salt loading, pressor and sympathetic responses to hypothalamic stimulation were reduced, instead of being increased. Since circulating plasma volume was increased in week 1, it was considered possible that reduced hypothalamic responsiveness was due to enhanced cardiopulmonary baroreflexes. Supporting this interpretation, bilateral vagotomy reversed the hypothalamic inhibition occurring in week 1. Although neither the site nor mechanism causing sympathetic hyperactivity has been determined, our results indicate that chronic dietary salt loading has biphasic effects on the ventromedial hypothalamus: an initial inhibition in the first week followed by stimulation thereafter. These results could mean that dietary salt loading eventually increases sympathetic activity and thereby induces hypertension by stimulating the ventromedial hypothalamus.

Antihypertensive and hypothalamic depressant effects of tripamide in spontaneously hypertensive rats

Summary: When tripamide was added to the food of spontaneously hypertensive rats (SHR), there were no appreciable effects on heart rate, body weight, or food intake. Tail-cuff systolic pressures measured weekly were also unaffected in normotensive control rats (WKY), but the elevation expected in SHR was significantly reduced. Pressor responses to hypothalamic stimulation were also reduced selectively only in SHR. A peripheral inhibition of cardiovascular reactivity was considered unlikely, since pressor responses to injected norepinephrine, tyramine, or vasopressin were unaltered. Diminished pressor responsiveness was considered to be due to concurrent reduction of central sympathetic vasomotor activity, because sympathetic nerve responses to hypothalamic stimulation were appreciably lessened in tripamide-treated SHR. Although neither the site nor the mechanism causing sympathetic inhibition was determined exactly, our results are in accord with the interpretation that anti-hypertensive effects of tripamide in SHR depend, at least partly, on sympathetic inhibition.