Catecholaminergic neurons in the comissural region of the nucleus of the solitary tract modulate hyperosmolality-induced responses.

Noradrenergic A2 neurons of the nucleus of the solitary tract (NTS) have been suggested to contribute to body fluid homeostasis and cardiovascular regulation. In the present study, we investigated the effects of lesions of A2 neurons of the commissural NTS (cNTS) on the c-Fos expression in neurons of the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, arterial pressure, water intake, and urinary excretion in rats with plasma hyperosmolality produced by intragastric 2 M NaCl (2 ml/rat). Male Holtzman rats (280-320 g) received an injection of anti-dopamine-ß-hydroxylase-saporin (12.6 ng/60 nl; cNTS/A2-lesion, n = 28) or immunoglobulin G (IgG)-saporin (12.6 ng/60 nl; sham, n = 24) into the cNTS. The cNTS/A2 lesions increased the number of neurons expressing c-Fos in the magnocellular PVN in rats treated with hypertonic NaCl (90 ± 13, vs. sham: 47 ± 20; n = 4), without changing the number of neurons expressing c-Fos in the parvocellular PVN or in the SON. Contrary to sham rats, intragastric 2 M NaCl also increased arterial pressure in cNTS/A2-lesioned rats (16 ± 3, vs. sham: 2 ± 2 mmHg 60 min after the intragastric load; n = 9), an effect blocked by the pretreatment with the vasopressin antagonist Manning compound (0 ± 3 mmHg; n = 10). In addition, cNTS/A2 lesions enhanced hyperosmolality-induced water intake (10.5 ± 1.4, vs. sham: 7.7 ± 0.8 ml/60 min; n = 8-10), without changing renal responses to hyperosmolality. The results suggest that inhibitory mechanisms dependent on cNTS/A2 neurons reduce water intake and vasopressin-dependent pressor response to an acute increase in plasma osmolality.

Inhibitory mechanism of the nucleus of the solitary tract involved in the control of cardiovascular, dipsogenic, hormonal, and renal responses to hyperosmolality.

The nucleus of the solitary tract (NTS) is the primary site of visceral afferents to the central nervous system. In the present study, we investigated the effects of lesions in the commissural portion of the NTS (commNTS) on the activity of vasopressinergic neurons in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, plasma vasopressin, arterial pressure, water intake, and sodium excretion in rats with plasma hyperosmolality produced by intragastric 2 M NaCl (2 ml/rat). Male Holtzman rats with 15-20 days of sham or electrolytic lesion (1 mA; 10 s) of the commNTS were used. CommNTS lesions enhanced a 2 M NaCl intragastrically induced increase in the number of vasopressinergic neurons expressing c-Fos in the PVN (28 ± 1, vs. sham: 22 ± 2 c-Fos/AVP cells) and SON (26 ± 4, vs. sham: 11 ± 1 c-Fos/AVP cells), plasma vasopressin levels (21 ± 8, vs. sham: 6.6 ± 1.3 pg/ml), pressor responses (25 ± 7 mmHg, vs. sham: 7 ± 2 mmHg), water intake (17.5 ± 0.8, vs. sham: 11.2 ± 1.8 ml/2 h), and natriuresis (4.9 ± 0.8, vs. sham: 1.4 ± 0.3 meq/1 h). The pretreatment with vasopressin antagonist abolished the pressor response to intragastric 2 M NaCl in commNTS-lesioned rats (8 ± 2.4 mmHg at 10 min), suggesting that this response is dependent on vasopressin secretion. The results suggest that inhibitory mechanisms dependent on commNTS act to limit or counterbalance behavioral, hormonal, cardiovascular, and renal responses to an acute increase in plasma osmolality.

Anti-hypertensive effect of hydrogen peroxide acting centrally.

Intracerebroventricular (icv) injection of hydrogen peroxide (H2O2) or the increase of endogenous H2O2 centrally produced by catalase inhibition with 3-amino-1,2,4-triazole (ATZ) injected icv reduces the pressor responses to central angiotensin II (ANG II) in normotensive rats. In the present study, we investigated the changes in the arterial pressure and in the pressor responses to ANG II icv in spontaneously hypertensive rats (SHRs) and 2-kidney, 1-clip (2K1C) hypertensive rats treated with H2O2 injected icv or ATZ injected icv or intravenously (iv). Adult male SHRs or Holtzman rats (n = 5-10/group) with stainless steel cannulas implanted in the lateral ventricle were used. In freely moving rats, H2O2 (5 µmol/1 µl) or ATZ (5 nmol/1 µl) icv reduced the pressor responses to ANG II (50 ng/1 µl) icv in SHRs (11 ± 3 and 17 ± 4 mmHg, respectively, vs. 35 ± 6 mmHg) and 2K1C hypertensive rats (3 ± 1 and 16 ± 3 mmHg, respectively, vs. 26 ± 2 mmHg). ATZ (3.6 mmol/kg of body weight) iv alone or combined with H2O2 icv also reduced icv ANG II-induced pressor response in SHRs and 2K1C hypertensive rats. Baseline arterial pressure was also reduced (-10 to -15 mmHg) in 2K1C hypertensive rats treated with H2O2 icv and ATZ iv alone or combined and in SHRs treated with H2O2 icv alone or combined with ATZ iv. The results suggest that exogenous or endogenous H2O2 acting centrally produces anti-hypertensive effects impairing central pressor mechanisms activated by ANG II in SHRs or 2K1C hypertensive rats.

Median preoptic nucleus excitatory neurotransmitters in the maintenance of hypertensive state.

The crucial role of the median preoptic nucleus (MnPO) in the maintenance of hydroelectrolytic balance and autonomic regulation have been highlighted. Recently, the participation of the MnPO in the control of sympathetic nerve activity was demonstrated in essential hypertension model. However, peculiarities on the neurochemical changes underlying the differential role of MnPO during hypertension remain to be clarified. Therefore, this study aimed to investigate the main excitatory pathways that modulate MnPO neurons in hypertensive rats. Spontaneously hypertensive rats (SHR) and rats submitted previously to the Goldblatt protocol (two kidneys; one clip; 2K1C) were used. Rats of both groups (250 to 350 g, n = 6) were anesthetized with urethane (1.2 g/kg,i.v.) and instrumented to record mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA). Nanoinjection (100 nl) of saline (NaCl, 150 mM), losartan (AT1 receptor antagonist; 10 mM) and kynurenic acid (glutamate receptor antagonist; 50 mM) into the MnPO were performed. In 2K1C rats, glutamatergic blockade promoted decreases in MAP and RSNA (-19.1 ± 0.9 mmHg, -21.6 ± 2.8%, p < 0.05) when compared to saline (-0.4 ± 0.6 mmHg, 0.2 ± 0.7%, p < 0.05). Angiotensinergic inhibition also reduced these parameters (-11.5 ± 1.2 mmHg, -10.5 ± 1.0%, p < 0.05) in 2K1C. In SHR, Kynurenic acid nanoinjections produced hypotension and sympathoinhibition (-21.0 ± 2.5 mmHg, -24.7 ± 2.4%, p < 0.05), as well losartan nanoinjections (-9.7 ± 1.2 mmHg; p < 0.05) and RSNA (-12.0 ± 2.4%, p < 0.05). These findings support the conclusion that a tonic excitatory neurotransmission exerted by angiotensin II, and mostly by glutamate in the MnPO could participate in the modulation of blood pressure and RSNA independent on whether hypertension is primarily neurogenic or is secondary to stenosis in renal artery.

Efferent pathways in sodium overload-induced renal vasodilation in rats.

Hypernatremia stimulates the secretion of oxytocin (OT), but the physiological role of OT remains unclear. The present study sought to determine the involvement of OT and renal nerves in the renal responses to an intravenous infusion of hypertonic saline. Male Wistar rats (280-350 g) were anesthetized with sodium thiopental (40 mg. kg(-1), i.v.). A bladder cannula was implanted for collection of urine. Animals were also instrumented for measurement of mean arterial pressure (MAP) and renal blood flow (RBF). Renal vascular conductance (RVC) was calculated as the ratio of RBF by MAP. In anesthetized rats (n = 6), OT infusion (0.03 µg • kg(-1), i.v.) induced renal vasodilation. Consistent with this result, ex vivo experiments demonstrated that OT caused renal artery relaxation. Blockade of OT receptors (OXTR) reduced these responses to OT, indicating a direct effect of this peptide on OXTR on this artery. Hypertonic saline (3 M NaCl, 1.8 ml • kg(-1) b.wt., i.v.) was infused over 60 s. In sham rats (n = 6), hypertonic saline induced renal vasodilation. The OXTR antagonist (AT; atosiban, 40 µg • kg(-1) • h(-1), i.v.; n = 7) and renal denervation (RX) reduced the renal vasodilation induced by hypernatremia. The combination of atosiban and renal denervation (RX+AT; n = 7) completely abolished the renal vasodilation induced by sodium overload. Intact rats excreted 51% of the injected sodium within 90 min. Natriuresis was slightly blunted by atosiban and renal denervation (42% and 39% of load, respectively), whereas atosiban with renal denervation reduced sodium excretion to 16% of the load. These results suggest that OT and renal nerves are involved in renal vasodilation and natriuresis induced by acute plasma hypernatremia.

Involvement of the intermediate nucleus of the lateral septal area on angiotensin II-induced dipsogenic and pressor responses.

Previous studies have shown that different parts of the septal area may have opposite roles in the control of water intake and cardiovascular responses. In the present study we investigated the effects of electrolytic lesions of the intermediate nucleus of the lateral septal area (LSI) on cardiovascular and dipsogenic responses to intracerebroventricular (icv) angiotensin II (ANG II) and water intake induced by other different stimuli. Male Holtzman rats (280-320 g of body weight, n=6-16/group) with sham or electrolytic lesions of the LSI and a stainless steel cannula implanted into the lateral ventricle (LV) were used. The LSI lesions did not affect body weight or daily water intake. However, LSI lesions reduced water intake and pressor responses induced by icv ANG II (4.10(-2) nmol). The LSI lesions also slightly reduced water intake induced by 24 h of water deprivation or isoproterenol (30 microg/kg) subcutaneously, but did not affect water intake induced by intragastric 2 ml of 2 M NaCl load. The results suggest that LSI is part of the forebrain circuitry activated by ANG II to produce pressor and dipsogenic responses. However, the same nucleus is not involved in the dipsogenic responses to central osmoreceptor activation.