Enhanced response from the caudal pressor area in spontaneously hypertensive rats.

The caudal pressor area (CPA), located in the caudal extension of the ventrolateral medulla, tonically activates the rostral ventrolateral medulla (RVLM) vasomotor neurons and regulates arterial pressure (AP) in normotensive animals. It is well established that sympathoexcitatory outflow from the RVLM in spontaneously hypertensive rats (SHR) is elevated compared to normotensive animals. Several studies have reported different cardiovascular responses to pharmacological alteration of the RVLM in SHR. Although the CPA may be one of the sources of presympathoexcitatory influence to the RVLM vasomotor drive in normotensive animals, it is unclear whether hypertensive animals such as SHR differ in their response to vasomotor drive evoked from the CPA. In this study, we examined whether sympathoexcitatory influence evoked from the CPA is enhanced in SHR. Local injection of glutamate into the CPA of chloralose-anesthetized male SHR elicited a substantially greater pressor response than in Wistar-Kyoto (WKY) rats, whereas the pressor response evoked by local injection of glutamate into the RVLM was the same in both strains. Furthermore, injection of glycine into the CPA decreased blood pressure to a greater extent in SHR than in WKY rats. These results suggest that the sympathoexcitatory influence of the CPA is enhanced in SHR. Therefore, the enhancement of sympathoexcitatory vasomotor drive evoked from the CPA may, at least in part, support elevated AP and regulate sympathetic tone in this hypertensive model.

High salt diet enhances cardiovascular responses from the nucleus tractus solitarius and ventrolateral medulla of Sprague-Dawley rats.

High salt intake has been shown to augment the sensitivity of rostral ventrolateral medulla (RVLM) sympathoexcitatory neurons. We examined the effects of 4 weeks of high dietary salt (8%) on the sensitivity of nucleus tractus solitarius (NTS) and caudal ventrolateral medulla (CVLM) in controlling RVLM. In chloralose-anesthetized Sprague-Dawley rats, high salt intake did not elevate baseline arterial pressure or heart rate (HR). In high-salt group, NTS, CVLM, and RVLM responses to glutamate were greater. NTS responses to acetylcholine or serotonin, which is independent of baroreflex, also were greater. Phenylephrine or nitroprusside (i.v.) elicited similar changes in arterial pressure and heart rate, the baroreflex sensitivity also was similar in both groups of rats. These results suggest that high salt intake augments the sensitivity of NTS and CVLM sending inhibitory input to RVLM. This presumably may inhibit the RVLM, thereby inhibiting the elevation of arterial pressure.

Effect of a high-salt diet on gamma-aminobutyric acid-mediated responses in the nucleus tractus solitarius of Sprague-Dawley rats.

Previous study using an indirect gamma-aminobutyric acid (GABA) agonist indicated that high salt intake enhances sensitivity of nucleus tractus solitarius (NTS) projecting inhibitory input to rostral ventrolateral medulla sympathoexcitatory neurons. We further investigated the relationship between salt intake and the GABA system in NTS. Sprague-Dawley (S-D) rats consuming high dietary salt (8%) or low dietary salt (0.3%) for 3 weeks were used. Under chloralose-anesthesia, baseline arterial pressure (AP) and heart rate (HR) were similar in both groups. Bilateral injection into NTS of nipecotic acid, GABA(A) receptor agonist (muscimol), or GABA(B) receptor agonist (baclofen) elicited greater pressor responses in high-salt group. GABA(A) receptor antagonist, bicuculline and GABA(B) receptor antagonist, CGP-35348 elicited greater depressor responses. Phenylephrine or nitroprusside (i.v.) elicited similar respective increases or decreases in AP in both groups. Baroreflex sensitivity was similar. Thus, high-salt intake enhances both GABA(A) receptor- and GABA(B) receptor-mediated responses within NTS, thereby inhibiting elevation of AP.

Enhanced angiotensin-mediated responses in the nucleus tractus solitarii of spontaneously hypertensive rats.

Studies using an AT(1) receptor antagonist, losartan, demonstrated that depressor and bradycardic responses to angiotensin II (Ang II) injection into the nucleus tractus solitarii (NTS) are mediated via those receptors. We further characterized Ang II-evoked cardiovascular responses in this nucleus in spontaneously hypertensive rats (SHR) using a new, selective AT(1) receptor antagonist, valsartan. In alpha-chloralose-anesthetized Sprague-Dawley (S-D) rats, Wistar-Kyoto (WKY) rats, and SHR, unilateral injection of Ang II into the NTS decreased arterial pressure (AP) and heart rate (HR). This response was eliminated by preinjection of valsartan. Depressor responses were much greater in SHR than in WKY rats. In normotensive rats, bilateral valsartan injection did not alter baseline AP or HR, or baroreceptor reflex index (BRI) calculated as the maximal change in HR (bpm) divided by phenylephrine- or nitroprusside-induced maximal change in mean AP (mmHg). In SHR, this treatment did not alter baseline HR and BRI, but significantly increased AP. Preinjection of valsartan did not alter injected glutamate effects in any strain. Thus, stimulation of AT(1) receptors within the NTS contributes to cardiovascular regulation independently of the baroreceptor reflex and the glutamatergic system. This angiotensinergic system in SHR acts tonically to reduce AP.

Ventrolateral medulla AT1 receptors support arterial pressure in Dahl salt-sensitive rats.

The present study addresses the hypothesis that angiotensin type 1 receptors (AT1Rs) in the rostral ventrolateral medulla (RVLM) contribute to the elevation of mean arterial pressure (MAP) in Dahl salt-sensitive (DS) rats fed a diet with a high NaCl content. Groups of DS or Dahl salt-resistant (DR) rats were fed diets containing either 0.3% NaCl (LNa) or 8% NaCl (HNa) for 3 weeks. Rats were anesthetized with alpha-chloralose, and the effects of microinjecting the AT1R antagonist valsartan (Val) or angiotensin II (Ang II) into the RVLM on MAP were measured. Bilateral injection of 100 pmol Val into the RVLM reduced the elevated MAP in the DS-HNa rats by approximately 35 mm Hg. In contrast, Val had no effect on MAP in DS-LNa rats. DR rats were normotensive on either diet; Val injection into the RVLM had no significant effect on MAP in DR-HNa rats but did evoke a small decrease in MAP in DR-LNa rats. Injection of Ang II into the RVLM increased arterial pressure in all groups, but the response was substantially larger in DS-HNa rats. Inhibition of neuronal function in the vicinity of the hypothalamic paraventricular nucleus, a possible source of innervation of the RVLM AT1R, by local injection with muscimol also produced a substantial decrease in MAP in DS-HNa rats but not in DS-LNa rats or DR rats. Thus, RVLM AT1Rs appear to contribute to salt-dependent hypertension in DS rats, and the paraventricular nucleus may be a source of this tonic activation.

Ventrolateral medulla AT1 receptors support blood pressure in hypertensive rats.

Angiotensin within the central nervous system appears to be important for the maintenance of hypertension in spontaneously hypertensive rats. This study addresses the hypothesis that blockade of AT1 receptors in the rostral ventrolateral medulla would decrease blood pressure in spontaneously hypertensive rats and that this tonically active AT1-mediated input to the rostral ventrolateral medulla arises from the hypothalamic paraventricular nucleus. Injection of the nonpeptide AT1 receptor antagonist valsartan bilaterally into the rostral ventrolateral medulla of choralose-anesthetized adult spontaneously hypertensive rats produced a dose-related decrease in mean arterial pressure, with a maximal effect of approximately 30 mm Hg. Inhibition of the paraventricular nucleus by local injection of muscimol elicited a similar response, which was inhibited by prior injection of valsartan into the rostral ventrolateral medulla. In contrast, in control Wistar-Kyoto rats, neither valsartan injected into the rostral ventrolateral medulla nor muscimol injected into the paraventricular nucleus had a substantial effect on arterial pressure. These data indicate that in spontaneously hypertensive rats but not in Wistar-Kyoto rats, rostral ventrolateral medulla vasomotor neurons are tonically excited by endogenous stimulation of AT1 receptors, and this input is apparently driven from the hypothalamus. These results suggest that the rostral ventrolateral medulla is one site that the brain renin-angiotensin system acts to maintain elevated blood pressure in spontaneously hypertensive rats.

Effect of phenylephrine injected into the nucleus tractus solitarius of Sprague-Dawley rats and spontaneously hypertensive rats.

In alpha-chloralose-anesthetized Sprague-Dawley (SD) rats with unilateral nucleus tractus solitarius (NTS) lesions, injection of the alpha(1)-adrenergic receptor agonist phenylephrine into the contralateral NTS dose-dependently increased arterial pressure (AP). Bunazosin (0.1 nmol) or prazosin (0.36 nmol), an alpha(1)-adrenergic receptor antagonist, also increased AP. When injected into the NTS, pre-treatment with phenylephrine (10 nmol) or both antagonists abolished the cardiovascular effects of glutamate and acetylcholine. In contrast, pre-treatment with prazosin or methylatropine did not alter the effect of phenylephrine. Phenylephrine (30 nmol) injected into the NTS abolished aortic depressor nerve (ADN) evoked-responses. The pressor effect of phenylephrine in the NTS was exaggerated in spontaneously hypertensive rats (SHR). These results suggest that when injected into the NTS, the effect of phenylephrine may be due to a baroreflex blockade resulting from direct modulatory actions or non-specific neuronal alterations rather than stimulating the alpha(1)-adrenergic receptor. Additionally, this effect is enhanced in SHR.