Role of lateral parabrachial nucleus in the inhibition of water intake produced by right atrial stretch.

Rats with either bilateral electrolytic or sham lesions of the ventrolateral portion of the lateral parabrachial nucleus (VLLPBN) were implanted with latex balloons that lay at the right superior vena cava/atrial junction (RSVC/AJ). Water intake in response to isoproterenol was measured both with and without inflation of the balloon. Water intake of the sham-lesioned rats was significantly depressed by balloon inflation during the first hour of the experiment. In contrast, water intake in the VLLPBN-lesioned rats was unaffected by balloon inflation. These results suggest that the VLLPBN is involved in the processing of afferent input from stretch-activated RSVC/AJ receptors.

Effects of lateral parabrachial nucleus lesions in chronic renal hypertensive rats.

Neuroanatomic studies describing forebrain projections to the lateral parabrachial nucleus suggest a central integrative role in cardiovascular regulation. We performed this study to examine the role of this pontine nucleus in the maintenance of one-kidney, figure-8 renal-wrap hypertension. Bilateral ibotenic acid ablation of the lateral parabrachial nucleus was performed 4 weeks after induction of hypertension or sham operation. In hypertensive rats, ablation produced a significant reduction in mean arterial pressure from 160 +/- 4 to 118 +/- 2 mm Hg and a transient but significant increase in heart rate from 381 +/- 5 to 408 +/- 8 beats per minute on the first day after ablation; arterial pressure returned to preablation values by day 5 after ablation. In sham-operated, normotensive animals, arterial pressure was not altered by ablation, and a transient but significant increase in heart rate from 384 +/- 8 to 419 +/- 7 beats per minute was again observed. Before ablation, trimethaphan administration produced a significantly greater drop in arterial pressure in hypertensive (delta-72.8 +/- 4.6 mm Hg) versus normotensive (delta-55.7 +/- 4.1 mm Hg) animals. This effect was eliminated on day 1 after ablation yet returned on day 4 after ablation. In blood samples obtained before ablation and on days 1 and 4 after ablation, circulating plasma catecholamine concentrations in both groups remained unchanged. These observations suggest that, because of possible alternate neural compensatory mechanisms, lateral parabrachial nucleus ablation produces a significant yet transient reversal of renal-wrap hypertension. Thus, the lateral parabrachial nucleus may contribute to the increased sympathetic nervous system function associated with this model.

Lateral parabrachial nucleus and angiotensin II-induced hypertension.

The objective of this study was to determine if ablation of the lateral parabrachial nucleus (LPBN) would prevent angiotensin II-induced hypertension in rats. Thirteen male Sprague-Dawley rats were studied. Bilateral electrolytic lesions in the LPBN were produced in six rats; the remaining seven rats were subjected to sham lesion surgery only. All rats were instrumented with vascular catheters and housed in metabolism cages. Daily measurements during the 16-day protocol included arterial pressure, heart rate, water intake, urine output, and urinary sodium excretion. Periodically throughout the protocol depressor responses to ganglion blockade and to blockade of V1-type vasopressin receptors also were measured. The protocol was divided into three control-period days, 10 days of continuous (24 hr/day) angiotensin II infusion (10 ng/min i.v.), and three recovery-period days. There were no significant differences between the two groups of rats for any variable during the control period. During angiotensin II infusion, sham-lesion rats exhibited a progressive increase in arterial pressure and the depressor response to ganglion blockade and a decrease in urinary sodium excretion. No other variable was significantly changed. In rats with LPBN lesions, arterial pressure was significantly increased only on days 1 and 3 of angiotensin II infusion. No other variable was affected. It was concluded that ablation of the LPBN in rats prevented sustained hypertension during intravenous infusion of angiotensin II by interfering with neurogenic pressor mechanisms normally activated by the peptide.

Parabrachial nucleus modulation of vasopressin release.

The present studies examine the contribution of the ventrolateral lateral parabrachial nucleus (VLLPBN) to the regulation of plasma arginine vasopressin (PAVP) release in response to either a baroreceptor or osmotic stimulus. These studies were carried out in rats with bilateral electrolytic lesions of the VLLPBN. Baroreceptor-induced stimulation of PAVP was achieved by decreasing blood pressure with combined blockade of the renin-angiotensin system with captopril (3 mg/kg iv) and the sympathetic nervous system with chlorisondamine, (11 mg/kg sc). Osmotic release of vasopressin was elicited by a 2-h intravenous infusion of hypertonic saline, (3.0 meq/ml, 0.01 ml/min). Blood pressure and heart rate were monitored throughout the experiments. Blood samples for determination of PAVP, plasma osmolality (posm), plasma sodium (PNa), and plasma potassium (PK) were taken before (base line) and after treatment in each study. The VLLPBN-lesioned rats secreted significantly more vasopressin in response to hypotension produced by combined renin-angiotensin and sympathetic nervous system blockade than did control rats. There was no significant difference between groups in Posm, PNa, or PK, or cardiovascular changes. In contrast, hypertonic saline infusion did not produce any differential changes between groups.

Brain stem mechanisms and the inhibition of angiotensin-induced drinking.

The present studies examine the effect of lesions of the ventrolateral region of the lateral parabrachial nucleus (VLLPBN) and of the area postrema and medial region of the nucleus of the solitary tract (AP/mNTS) on water intake induced by intracerebroventricular administration of angiotensin II (ANG II) and of the cholinergic receptor agonist, carbachol. Water intake was measured in rats with bilateral electrolytic lesions of the VLLPBN or thermocautery ablation of the AP/mNTS after intracerebroventricular delivery of ANG II (50 and 100 ng/2 microliter), carbachol (100 and 250 ng/2 microliter), and isotonic saline (2 microliter). Rats with lesions of the VLLPBN drank significantly more water during a 30-min test period to both doses of ANG II, but not to carbachol, than did sham lesion rats. Similarly, AP/mNTS lesion rats drank significantly more than sham lesion animals in response to the high dose of ANG II but not to carbachol. These results suggest that the previously reported exaggerated drinking responses to systemically administered ANG II demonstrated by rats with either VLLPBN or AP/mNTS lesions is not the result of a direct peripheral action of the octapeptide. Furthermore, the similarity of the induced drinking responses produced by these two lesions suggests that the AP/mNTS and the VLLPBN may be linked in a common thirst-mediating pathway.

Lesions in lateral parabrachial nucleus enhance drinking to angiotensin II and isoproterenol.

The lateral parabrachial nucleus (LPBN) has been shown to be anatomically linked to a number of forebrain nuclei and medullary structures implicated in the control of body fluid balance and cardiovascular regulation. Although these connections suggest a role for the LPBN in body fluid homeostasis, there is currently little or no physiological or behavioral data to support this notion. The purpose of the present series of experiments was to determine the importance of the ventrolateral region of the LPBN (VLLPBN) in the behavioral response to various thirst challenges. Rats with electrolytic lesions of the VLLPBN and control rats were studied after administration of angiotensin II (ANG II) (1.5 and 3.0 mg/kg), isoproterenol (30 and 100 micrograms/kg), polyethylene glycol (20%) and hypertonic saline (4 and 12%). It was found that rats with lesions drank more in response to ANG II and isoproterenol administration than did control animals.

Transection of subfornical organ neural connections diminishes the pressor response to intravenously infused angiotensin II.

Knife-cut lesions were used to assess the participation of the subfornical organ (SFO) in the central pressor action of intravenously administered angiotensin. Knife-cuts of the ventral stalk of the SFO significantly attenuated pressor responses during infusion of 3 doses of angiotensin, although responses to bolus injections were unaffected. These results are consistent with previous work in implicating the SFO as an important mediator of the central pressor action of circulating angiotensin.