Central blockade of nitric oxide synthesis reduces moxonidine-induced hypotension

1 Nitric oxide (NO) and alpha(2)-adrenoceptor and imidazoline agonists such as moxonidine may act centrally to inhibit sympathetic activity and decrease arterial pressure.2 In the present study, we investigated the effects of pretreatment with L-NAME ( NO synthesis inhibitor), injected into the 4th ventricle (4th V) or intravenously (i.v.), on the hypotension, bradycardia and vasodilatation induced by moxonidine injected into the 4th V in normotensive rats.3 Male Wistar rats with a stainless steel cannula implanted into the 4th V and anaesthetized with urethane were used. Blood flows were recorded by use of miniature pulsed Doppler flow probes implanted around the renal, superior mesenteric and low abdominal aorta.4 Moxonidine (20 nmol), injected into the 4th V, reduced the mean arterial pressure (-42+/-3 mmHg), heart rate (-22+/-7 bpm) and renal (-62+/-15%), mesenteric (-41+/-8%) and hindquarter (-50+/-8%) vascular resistances.5 Pretreatment with L-NAME (10 nmol into the 4th V) almost abolished central moxonidine-induced hypotension (-10+/-3 mmHg) and renal (-10+/-4%), mesenteric (-11+/-4%) and hindquarter (-13+/-6%) vascular resistance reduction, but did not affect the bradycardia (-18+/-8 bpm).6 the results indicate that central NO mechanisms are involved in the vasodilatation and hypotension, but not in the bradycardia, induced by central moxonidine in normotensive rats. British Journal of Pharmacology (2004).

Moxonidine and rilmenidine injected into the medial septal area reduces the salivation induced by pilocarpine

We determined the effects of moxonidine and rilmenidine 20 mol (alpha(2)-adrenergic and imidazoline receptor agonists) injected into the medial septal area (MSA) on the pilocarpine-induced salivation, when injected intraperitoneally (i.p.), of male Holtzman rats weighing 250300 g, with stainless-steel cannula implanted into the MSA. The rats were anesthetized with zoletil 50 mg kg(-1) b.wt. (tiletamine chloridrate 125.0 mg and zolazepan chloridrate 125.0 mg) into quadriceps muscle intramuscularly (IM), saliva was collected using pre-weighed small cotton balls inserted in the animal's mouth. The pre-treatment with moxonidine injected into the MSA reduced the salivation induced by pilocarpine (1 mg kg(-1)) injected i.p. (12 +/- 3 mg min(-1)) vs. control (99 +/- 9 mg min(-1)). The pre-treatment with rilmenidine 40 nmol also reduced the salivation induce by pilocarpine injected i.p. (20 +/- 5 mg min(-1)) vs. control (94 +/- 7 mg min(-1)). Idazoxan 40 nmol (imidazoline receptor antagonist) injected into the MSA previous to moxonidine and rilmenidine partially blocked the effect of moxonidine and totally blocked the rilmenidine effect in pilocarpine-induced salivation injected i.p. (60 +/- 8 and 95 +/- 10 mg min(-1), respectively). Yohimbine 40 nmol (alpha(2)-adrenergic receptor antagonist) injected into the MSA previously to moxonidine and rilmenidine partially blocked the moxonidine effect but produced no change on the rilmenidine effect on i.p. pilocarpine-induced salivation (70 +/- 6 and 24 +/- 6 mg min(-1), respectively). Injection of these alpha(2)-adrenergic and imidazoline agonists and antagonists agents i.p. produced no change on i.p. pilocarpine-induced salivation. These results show that central, but not peripheral, injection of alpha(2)-adrenergic and imidazoline agonists' agents inhibit pilocarpine-induced salivation. Idazoxan, an imidazoline receptor antagonist, totally inhibits the rilmenidine effect and partially inhibits the moxonidine effect on pilocarpine-induced salivation. Yohimbine produced no change on rilmenidine effect but partially inhibited the moxonidine effect. Both of these antagonists when injected into the MSA previous to pilocarpine i.p. potentiated the sialogogue effect of pilocarpine. The results suggest that alpha(2)-adrenergic/imidazoline receptor of the MSA when stimulated blocked pilocarpine-induced salivation in rats when injected intraperitonially These receptors of the medial septal area have an inhibitory mechanism on salivary secretion. (C) 2004 Elsevier B.V. All rights reserved.

Effects of V-1 and angiotensin receptor subtypes of the paraventricular nucleus on the water intake induced by vasopressin injected into the lateral septal area

In this study, we investigated the influence of d(CH2)(5)-Tyr (Me)-AVP (AAVP) an antagonist of V-1 receptors of arginine(8)-vasopressin (AVP) and the effects of losartan and CGP42112A (selective ligands of the AT, and AT, angiotensin receptors, respectively) injections into the paraventricular nucleus (PVN) on the thirst effects of AVP stimulation of the lateral septal area (LSA). AVP injection into the LSA increased the water intake in a dose-dependent manner. AAVP injected into the PVN produced a dose-dependent reduction of the drinking responses elicited by LSA administration of AVP. Both the AT(1) and AT(2) ligands administered into the PVN elicited a concentration-dependent inhibition in the water intake induced by AVP injected into the LSA, but losartan was more effective than CGP42112A the increase in the AVP response. These results indicate that LSA dipsogenic effects induced by AVP are mediated primarily by PVN AT(1) receptors. However, doses of losartan were more effective when combined with CGP42112A than when given alone, suggesting that the thirst induced by AVP injections into LSA may involve activation of multiple angiotensin II (ANG II) receptor subtypes. These results also suggests that facilitatory effects of AVP on water intake into the LSA are mediated through the activation of V-receptors and that the inhibitory effect requires V-receptors. Based on the present findings, we suggest that the administration of AVP into the LSA may play a role in the PVN control of water control. (C) 2003 Elsevier B.V. All rights reserved.

Effects of subtypes of adrenergic and angiotensinergic antagonists on the water and sodium intake induced by adrenaline injected into the paraventricular nucleus

The present experiments were conducted to investigate die role of the alpha(1A)-, alpha(1B)-, beta(1)-, beta(2)-adrenoceptors, and the effects of losartan and CGP42112A (selective ligands of the AT(1) and AT(2) angiotensin receptors, respectively) on the water and sodium intake elicited by paraventricular nucleus (PVN) injection of adrenaline. Male Holtzman rats with a stainless steel cannula implanted into the PVN were used. The ingestion of water and sodium was determined in separate groups submitted to water deprivation or sodium depletion with the diuretic furosemide (20 mg/rat). 5-Methylurapidil (an alpha(1A)-adrenergic antagonist) and ICI-118,551 (a beta(2)-adrenergic antagonist) injected into the PVN produced a dose-dependent increase, whereas cyclazosin (an alpha(1B)-adrenergic antagonist) and atenolol (a beta(1)-adrenergic antagonist) do not affect the inhibitory effect of water intake induced by adrenaline. on the other hand, the PVN administration of adrenaline increased the sodium intake in a dose-dependent manner. Previous injection of the alpha(1A) and beta(1) antagonists decreased, whereas injection of the alpha(1B) and beta(2) antagonists increased the salt intake induced by adrenaline. In rats with several doses of adrenaline into PVN, the previous administration of losartan increased in a dose-dependent manner the inhibitory effect of adrenaline and decreased the salt intake induced by adrenaline, while PVN CGP42112A was without effect. These results indicate that both appetites are mediated primarily by brain AT(1) receptors. However, the doses of losartan were more effective when combined with the doses of CGP42112A than given alone p < 0.05, suggesting that the water and salt intake effects of PVN adrenaline may involve activation of multiple angiotensin II (ANG II) receptors subtypes. (C) 2003 Elsevier B.V. All rights reserved.

Cardiovascular responses to hydrogen peroxide into the nucleus tractus solitarius

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Central muscarinic receptor subtypes involved in pilocarpine-induced salivation, hypertension and water intake

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Central mechanisms involved in pilocarpine-induced pressor response

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influence of arginine vasopressin receptors and angiotensin receptor subtypes on the water intake and arterial blood pressure induced by vasopressin injected into the lateral septal area of the rat

In this study we investigated the influence of d(CH2)(5)-Tyr(Me)-[Arg(8)]vasopressin (AAVP) and [adamanteanacetyl(1),0-ET-DTyr(2), Val(4), aminobutyryl(6), Arg(8,9)]-[Arg(8)]vasopressin (ATAVP), which are antagonists of vasopressin V-1 and V-2 receptors, and the effects of losartan, a selective angiotensin AT(1) receptor antagonist, and CGP42112A, a selective AT(2) receptor antagonist, injected into the lateral septal area (LSA) on thirst and hypertension induced by [Arg(8)]vasopressin (AVP). AAVP and ATAVP injected into the LSA reduced the drinking responses elicited by injecting AVP into the LSA. Both the AT(1) and AT(2) ligands administered into the LSA elicited a concentration-dependent decrease in the water intake induced by AVP injected into the LSA, but losartan was more effective than CGP42112A. The increase in MAP, due to injection of AVP into the LSA, was reduced by prior injection of AAVP from 18 +/- 1 to 6 +/- 1 mm Hg. Losartan injected into the LSA prior to AVP reduced the increase in MAP to 7 +/- 0.8 mm Hg. ATAVP and CGP42112A produced no changes in the pressor effect of AVP. These results suggest that the dipsogenic effects induced by injecting AVP into the LSA were mediated primarily by AT(1) receptors. However, doses of losartan were more effective when combined with CGP42112A than when given alone, suggesting that the thirst induced by AVP injections into LSA may involve activation of multiple AVP and angiotensin II receptor subtypes. The pressor response of AVP was reduced by losartan and by AAVP. CGP42112A and ATAVP did not change the AVP pressor response. These results suggest that facilitator effects of AVP on water intake are mediated through the activation of V-1 receptors and that the inhibitory effect requires V-2 receptors. The involvement of AT(1) and AT(2) receptors can be postulated. Based on the present findings, we suggest that the AVP in the LSA may play a role in the control of water and arterial blood pressure balance. (C) 2004 Elsevier B.V. All rights reserved.

LESIONS OF THE LATERAL HYPOTHALAMUS IMPAIR THE PRESSOR-RESPONSE TO CLONIDINE INJECTED INTO THE MEDIAL SEPTAL AREA OF CONSCIOUS RATS

The central injection of clonidine (an alpha-2-adrenoceptor agonist) in conscious normotensive rats produces hypertensive responses and bradycardia. The present study was performed to investigate the effect of electrolytic lesions of the lateral hypothalamus (LH) on the pressor and bradycardic responses induced by clonidine injected into the medial septal area (MSA) in conscious and unrestrained rats. Male Holtzman rats weighing 250-300 g were used. Mean arterial pressure and heart rate were recorded in sham- or bilateral LH-lesioned rats with a cerebral stainless steel cannula implanted into the MSA. The injection of clonidine (40 nmol/mu-l) into the MSA of sham rats (N = 8) produced a pressor response (36 +/- 7 mmHg, P<0.05) and bradycardia (-70 +/- 13 bpm, P<0.05) compared to saline. Fourteen days after LH-lesion (N = 9) the pressor response was reduced (9 +/- 10 mmHg, P<0.05) but no change was observed in the bradycardia (-107 +/- 24 bpm). These results show that LH is an important area involved in the pressor response to clonidine injected into the MSA of rats.

Antagonism of clonidine injected intracerebroventricularly in different models of salt intake

Clonidine, an alpha 2-adrenergic agonist, injected into the brain inhibits salt intake of animals treated by the diuretic model of sodium depletion. In the present study, we address the question of whether central injection of clonidine also inhibits salt intake in animals deprived of water or in the need-free state. Saline or clonidine (30 nmol) was injected into the anterior third ventricle of 24-h sodium-depleted (furosemide + removal of ambient sodium), of 24-h water-deprived and of normovolemic (need-free state) adult male rats, Clonidine injected intracerebroventricularly (icv) inhibited the 1.5% NaCl intake for 120 min by 50 to 90% in every model tested. Therefore, different models of salt intake are inhibited by icv injection of clonidine, Idazoxan, an alpha 2-adrenergic antagonist, injected icy at a dose of 160 nmol, inhibited the effect of clonidine only in the furosemide + removal of ambient sodium model of salt intake. This indicates that the antagonism of this effect by idazoxan is dependent on the body fluid/sodium status of the animal.

Evaluation of shear bond strength at the interface of two porcelains and pure titanium injected into the casting mold at three different temperatures

Statement of problem. Titanium has physical and mechanical properties, which have led to its increased use in dental prostheses despite casting difficulties due to high melting point and formation of oxide layers which affect the metal-ceramic bond strength.Purpose. This in vitro study evaluated the shear bond strength of the interface of 2 dental porcelains and pure titanium injected into a mold at 3 different temperatures.Material and methods. Using commercially pure (cp) titanium bars (Titanium, Grade I) melted at 1668degreesC and cast at mold temperatures of 430degreesC, 700degreesC or 900degreesC, 60 specimens were machined to 4 x 4 mm, with a base of 5 x 1 mm. The 4-mm surfaces were airborne-particle abraded with 100 mum aluminum oxide before applying and firing the bonding agent and evaluating the 2 porcelains (Triceram/Triline ti and Vita Titankeramik). Ten specimens were prepared for each temperature and porcelain combination Shear bond testing was performed in a universal testing machine, with a 500-kg load cell and crosshead speed of 0.5 mm/min. The specimens were loaded until failure. The interfaces of representative fractured specimens of each temperature were examined with a scanning electron microscope (SEM) and energy dispersive spectrometer (EDS). Data for shear bond strength (MPa) were statistically analyzed by 2-way ANOVA and the Tukey test (alpha = .05).Results. The results showed significant differences for the metal/porcelain interaction effect (P = .0464). There were no significant differences for the 2 porcelains (P = .4250). The Tukey test showed a significant difference between the pair cp Ti 430degreesC Triceram and cp Ti 900degreesC Triceram, with respective mean values and SDs of 59.74 +/- 11.62 and 34.03 +/- 10.35 MPa.Conclusion. Triceram porcelain showed a bond strength decrease with an increase in the mold temperature for casting titanium. The highest bond strength for Vita porcelain and the best metal-ceramic interface observed with the SEM were found with the mold temperature of 700degreesC.