Interaction between paraventricular nucleus and septal area in the control of physiological responses induced by angiotensin II

Abstract

We determined the effects of losartan (40 nmol) and PD 123319 (40 nmol) (both non-peptides and selective antagonists of the AT 1 and AT 2 angiotensin receptors, respectively), and [Sar 1 , Ala 8 ] angiotensin II (ANG II) (40 nmol) (a non-selective peptide antagonist of angiotensin receptors) injected into the paraventricular nucleus (PVN) on the water and salt appetite, diuresis and natriuresis and mean arterial pressure (MAP) induced by administration of 10 nmol of ANG II into the medial septal area (MSA) of male Holtzman rats weighing 250-300 g. The volume of drug solution injected was 0.5 µl over a period of 10-15 s. The responses were measured over a period of 120 min. ANG II alone injected into the MSA induced an increase in all the above parameters (8.1 ± 1.2, 1.8 ± 0.3, and 17.1 ± 1.0 ml, 217 ± 25 µEq/120 min, and 24 ± 4 mmHg, respectively, N = 10-12) compared with vehicle-treated rats (1.4 ± 0.2, 0.6 ± 0.1, and 9.3 ± 0.5 ml, 47 ± 5 µEq/120 min, and 4.1 ± 0.8 mmHg, respectively, N = 10-14). Pretreatment with losartan and [Sar 1 , Ala 8 ] ANG II completely abolished the water and sodium intake, and the pressor increase (0.5 ± 0.2, 1.1 ± 0.2, 0.5 ± 0.2, and 0.8 ± 0.2 ml, and 1.2 ± 3.9, 31 ± 4.6 mmHg, respectively, N = 9-12), whereas losartan blunted the urinary and sodium excretion induced by ANG II (13.9 ± 1.0 ml and 187 ± 10 µEq/120 min, respectively, N = 9). Pretreatment with PD 123319 and [Sar 1 , Ala 8 ] ANG II blocked the urinary and sodium excretion (10.7 ± 0.8, 9.8 ± 0.7 ml, and 67 ± 13 and 57 ± 17 µEq/120 min, respectively, N = 9), whereas pretreatment with PD 123319 partially blocked the water and sodium intake, and the MAP induced by ANG II administration (2.3 ± 0.3, 1.1 ± 0.1 ml, and 12 ± 3 mmHg, respectively, N = 9-10). These results suggest the angiotensinergic effect of the MSA on the AT 1 and AT 2 receptors of the PVN in terms of water and sodium homeostasis and MAP modulation.

Role of nitric oxide of the median preoptic nucleus (MnPO) in the alterations of salivary flow, arterial pressure and heart rate induced by injection of pilocarpine into the MnPO and intraperitoneally

“…Pilocarpine injected ip produced a copious salivary flow that was potentiated by the previous central injection of L-NAME into the MnPO. Therefore we postulate that the systemic effects of pilocarpine on salivary flow and cardiovascular regulation are influenced by central NO release, in agreement with the results reported by others (16,17). Pilocarpine injected ip decreased the MAP and increased the HR, with an opposite effect when injected into the MnPO, where it acted by increasing salivary flow and blood pressure, with a decrease in HR.…”

“…Pilocarpine has been used extensively as the best sialogogue rather than other cholinomimetic agents but produces cardiovascular alterations as side effects. NO plays an important role in the hydromineral and cardiovascular regulation induced by angiotensin (16,17). Different data indicate that the median preoptic nucleus (MnPO) is indeed the target of afferents from osmosensitive and barosensitive systems involved in fluid homeostasis and cardiovascular regulation (18)(19)(20).…”

Immunohistochemical Localization ofAT1a,AT1b<

“…With the discovery of these multiple subtypes of Ang II receptors, pharmacological studies revealed that the AT 1 subtype mediated both aldosterone [20] and epinephrine [21] release as well as pressor [22, 23], dipsogenic [22–24], and sodium appetite [24–26] responses to Ang II. The localization of AT 1 receptors in the rat brain regions mediating pressor and dipsogenic actions of Ang II, such as the subfornical organ (SFO), median preoptic nucleus (MnPO), organum vasculosum of the lamina terminalis (OVLT) paraventricular nucleus of the hypothalamus (PVN), nucleus of the solitary tract (NTS), and area postrema [27–29] is consistent with this role.…”

Medial Septal Area Vasopressin Receptor Subtypes in the Regulation of Urine and Sodium Excretion in Rats

“…The existence of a separate and distinct RAS exists within the mammalian brain is now well established (16). The injection of angiotensin II into the MSA increases sodium excretion (17, 18) and a relationship was determined between the vasopressinergic and angiotensinergic control of water and sodium intake, as well as of medial arterial pressure regulation in the MSA (19, 20).…”