Modulation of coronary flow and cardiomyocyte size by sensory fibers

Cardiac tissue is densely innervated by sensory neurons that an believed to play important modulatory roles in cardiac functions. In this study, pretreatment of neonate mts with capsaicin was performed. In adult rats, cardiomyocyte size and amount of fibrous tissue in left ventricles as well as in vitro coronary flow were evaluated, the chronotropic and inotropic responses to beta-adrenoceptor agonists (norepinephrine and isoproterenol), muscarinic agonists (carbachol and pilocarpine), and calcitonin gene-related peptide (CGRP) were also investigated with the use of the isolated right atria preparation. Capsaicin pretreatment significantly (P<0.05) reduced both basal coronary flow (18% reduction) and cardiomyocyte size (34% reduction) without affecting the amount of fibrous tissues in the left ventricles. The positive inotropic and chronotropic effects in response to norepinephrine in the isolated rat heart did not significantly differ between control and capsaicin-treated rats, Similarly, the positive chronotropic effects in response to norepinephrine, isoproterenol, and CGRP as well as the negative chronotropic responses to carbachol and pilocarpine in the isolated light atria were not affected by capsaicin pretreatment, Our data are consistent with the suggestion that reductions of both basal coronary flow and cardiomyocyte size seen in hearts from capsaicin-pretreated rats may be consequences of CGRP depletion. The cardiomyocyte size reduction produced by capsaicin treatment may be related to a modulatory role of CGRP as a growth factor.

Chronotropic response of beta-adrenergic-, muscarinic-, and calcitonin gene-related peptide-receptor agonists in right atria from neonatal capsaicin-treated rats

We evaluated the potency of isoproterenol, carbachol, pilocarpine and calcitonin gene-related peptide (CGRP) in the rat right atria at 30, 60 and 90 days after neonatal capsaicin treatment. Neonatal rats were pretreated on the second day of life with capsaicin (50 mg/kg). The capsaicin pretreatment caused a five-fold rightward shift at the pEC(50) level on the concentration-response curves to isoproterenol in 30-day-old rats. Propranolol (10 mg/kg, given 15 min prior to capsaicin treatment) prevented this subsensitivity. No changes in the potency of isoproterenol were observed at 60 and 90 days after capsaicin pretreatment. The potency and maximal responses of CGRP in the right atria in 30-day-old rats were significantly higher than in 60- and 90-day-old rats; however, no differences were found between control and capsaicin groups. The potency and maximal responses to carbachol and pilocarpine were not changed in all groups. The neonatal capsaicin treatment reduced by about 74% the CGRP content in the heart in all groups. In summary, capsaicin treatment in newborn rats produces a desensitization of chronotropic response mediated by beta-adrenoceptors in isolated right atria from 30-day-old rats possibly due to a massive release of catecholamines. (C) 2002 Elsevier B.V. Ireland Ltd. All rights reserved.

Long-term nitric oxide inhibition and chronotropic responses in rat isolated right atria

The long-term administration of nitric oxide synthesis inhibitors induces arterial hypertension accompanied by left ventricular hypertrophy and myocardial ischemic lesions. Because the enhancement of sympathetic drive has been implicated in these phenomena, the current study was performed to determine the potency of β-adrenoceptor agonists and muscarinic agonists on the spontaneous rate of isolated right atria from rats given long-term treatment with the nitric oxide inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME). Atrial lesions induced by long-term treatment with L-NAME were also evaluated. Long-term L-NAME treatment caused a time-dependent, significant (P<0.05) increase in tail-cuff pressure compared with control animals. Our results showed that the potency of isoproterenol, norepinephrine, carbachol, and pilocarpine in isolated right atria from rats given long-term treatment with L-NAME for 7, 15, 30, and 60 days was not affected as compared with control animals. Addition of L-NAME in vitro (100 μmol/L) affected neither basal rate nor chronotropic response for isoproterenol and norepinephrine in rat heart. Stereological analysis of the right atria at 15 and 30 days revealed a significant increase on amount of fibrous tissues in L-NAME- treated groups (27±2.3% and 28±1.3% for 15 and 30 days, respectively; P<0.05) as compared with the control group (22±1.1%). Our results indicate that nitric oxide does not to interfere with β-adrenoceptor-mediated and muscarinic receptor-mediated chronotropic responses.

Neuroendocrine alterations impair enamel mineralization, tooth eruption and saliva in rats.

Neonatal administration of monosodium glutamate (MSG) in rats causes definite neuroendocrine disturbances which lead to alterations in many organ systems. The possibility that MSG could affect tooth and salivary gland physiology was examined in this paper. Male and female pups were injected subcutaneously with MSG (4 mg/g BW) once a day at the 2nd, 4th, 6th, 8th and 10th day after birth. Control animals were injected with saline, following the same schedule. Lower incisor eruption was determined between the 4th and the 10th postnatal days, and the eruption rate was measured between the 43rd and the 67th days of age. Pilocarpine-stimulated salivary flow was measured at 3 months of age; protein and amylase contents were thereby determined. The animals treated with MSG showed significant reductions in the salivary flow (males, -27%; females, -40%) and in the weight of submandibular glands (about -12%). Body weight reduction was only about 7% for males, and did not vary in females. Saliva of MSG-treated rats had increased concentrations of total proteins and amylase activity. The eruption of lower incisors occurred earlier in MSG-treated rats than in the control group, but on the other hand the eruption rate was significantly slowed down. The incisor microhardness was found to be lower than that of control rats. Our results show that neonatal MSG treatment causes well-defined oral disturbances in adulthood in rats, including salivary flow reduction, which coexisted with unaltered protein synthesis, and disturbances of dental mineralization and eruption. These data support the view that some MSG-sensitive hypothalamic nuclei have an important modulatory effect on the factors which determine caries susceptibility.

Central nifedipine-induced alterations in salivary flow and compounds: Role of nitric oxide

The aim of this study was to examine the role of nifedipine and Nitric Oxide (NO) on salivary flow and compounds (salivary amylase, saliva total proteins, saliva calcium, sodium and potassium). Male Holtzman rats weighting 200-250 g were anesthetized with zoletil 50 mg kg -1 (tiletamine chloridrate 125.0 mg and zolazepan chloridrate 125.0 mg) into quadriceps muscle and stainless steel cannulas were implanted into their lateral ventricle of the brain (LV). Animals in divided group were injected with nifedipine (50 μg μL -1) alone and in combination with 7-nitroindazol (7-NIT) (40 μg μL -1), neuronal NO Sinthase Inhibitor (nNOSI) and Sodium Nitroprussate (SNP) (30 μg μL -1) NO donor agent. As a secretory stimuli, pilocarpine dissolved in isotonic was administered intraperitoneally (ip) at a dosage of 10 mg kg -1 body weight. Saliva was collected for 7 min with four cotton balls weighing approximately 20 mg each, two of which were placed on either side of the oral cavity, with the other two placed under the tongue. Nifedipine treatment induced a reduction in saliva secretion rate and concentration of amylase, total protein and calcium without changes in sodium and potassium concentration in comparison with controls. Co-treatment of animals with nifedipine and SNP retained flow rate and concentration of amylase, total protein and calcium in normal levels. Co-treatment of animals with nifedipine and 7-NIT potentiated the effect of nifedipine on the reduction of saliva secretion and concentrations of amylase, total protein and calcium. Nifedipine (dihydroperidine) calcium-channel blocker widely in use is associated with salivary dysfunction acting in the central nervous system structures. NO might be the mechanism for protective effect against the nifedipine-induce salivary dysfunction, acting in the CNS. © 2006 Asian Network for Scientific Information.

A meniralização dental e a atividade salivar estão reduzidas em filhotes de ratas espontaneamente hipertensas (SHR)

Several pathologies have been diagnosed in children of hypertensive mothers; however, some studies that evaluated the alterations in their oral health are not conclusive. This study analyzed the salivary gland activity and dental mineralization of offsprings of spontaneously hypertensive rats (SHR). Thirty-day-old SHR males and Wistar rats were studied. The salivary flow was evaluated by injection of pilocarpine, the protein concentration and salivary amylase activity, by the Lowry method and kinetic method at 405 nm, respectively. Enamel and dentin mineralization of the mandibular incisors was quantified with aid of the microhardness meter. The results were analyzed by the ANOVA or Student's t test (p<0.05). It was noticed that the salivary flow rate (0.026 mL/min/100 g±0.002) and salivary protein concentration (2.26mg/mL±0.14) of SHR offspring were reduced compared to Wistar normotensive offspring (0.036 mL/min/100 g±0.003 and 2.91 mg/mL±0.27, respectively), yet there was no alteration in amylase activity (SHR: 242.4 U/mL±36.9; Wistar: 163.8 U/mL±14.1). Microhardness was lower both in enamel (255.8 KHN±2.6) and dentin (59.9 KHN±0.8) for the SHR teeth compared to the Wistar teeth (enamel: 328.7 KHN±3.3 and dentin: 67.1 KHN±1.0). These results suggest that the SHR offspring are more susceptible to development of pathologies impairing oral health, once they presented lesser flow and salivary protein concentration and lower dental mineralization.

Activation of central aα-adrenoceptors mediates salivary gland vasoconstriction

Objective: Peripheral treatment with the cholinergic agonist pilocarpine increases salivary gland blood flow and induces intense salivation that is reduced by the central injection of moxonidine (aα-adrenoceptors/ imidazoline agonist). In the present study, we investigated the effects of the intracerebroventricular (i.c.v.) injection of pilocarpine alone or combined with moxonidine also injected i.c.v. On submandibular/sublingual gland (SSG) vascular resistance. In addition, the effects of these treatments on arterial pressure, heart rate and on mesenteric and hindlimb vascular resistance were also tested. Design: Male Holtzman rats with stainless steel cannula implanted into lateral ventricle and anaesthetized with urethane + α-chloralose were used. Results: Pilocarpine (500 nmol/1 μl) injected i.c.v. Reduced SSG vascular resistance and increased arterial pressure, heart rate and mesenteric vascular resistance. Contrary to pilocarpine alone, the combination of moxonidine (20 nmol/1 μl) and pilocarpine injected i.c.v. Increased SSG vascular resistance, an effect abolished by the pre-treatment with the α2-adrenoceptor antagonist yohimbine (320 nmol/2 μl). The increase in arterial pressure, heart rate and mesenteric resistance was not modified by the combination of moxonidine and pilocarpine i.c.v. Conclusion: These results suggest that the activation of central α2- adrenoceptors may oppose to the effects of central cholinergic receptor activation in the SSG vascular resistance. © 2012 Elsevier Ltd. All rights reserved.

Estudo da atividade salivar em ratos espontaneamente hipertensos (SHR)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Efeito do tratamento crônico com fluoreto na atividade salivar, ossos e dentes de ratos espontaneamente hipertensos (SHR)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Efeito da hipertensão e do atenolol sobre a atividade salivar e a microdureza dental: estudo experimental em filhotes de ratas espontaneamente hipertensas (SHR)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Sodium intake combining cholinergic activation and noradrenaline into the lateral parabrachial nucleus

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

Dental mineralization and salivary activity are reduced in offspring of spontaneously hypertensive rats (SHR)

Several pathologies have been diagnosed in children of hypertensive mothers; however, some studies that evaluated the alterations in their oral health are not conclusive. This study analyzed the salivary gland activity and dental mineralization of offsprings of spontaneously hypertensive rats (SHR). Thirty-day-old SHR males and Wistar rats were studied. The salivary flow was evaluated by injection of pilocarpine, the protein concentration and salivary amylase activity, by the Lowry method and kinetic method at 405 nm, respectively. Enamel and dentin mineralization of the mandibular incisors was quantified with aid of the microhardness meter. The results were analyzed by the ANOVA or Student's t test (p<0.05). It was noticed that the salivary flow rate (0.026 mL/min/100 g ± 0.002) and salivary protein concentration (2.26 mg/mL ± 0.14) of SHR offspring were reduced compared to Wistar normotensive offspring (0.036 mL/min/100 g ± 0.003 and 2.91 mg/mL ± 0.27, respectively), yet there was no alteration in amylase activity (SHR: 242.4 U/mL ± 36.9; Wistar: 163.8 U/mL ± 14.1). Microhardness was lower both in enamel (255.8 KHN ± 2.6) and dentin (59.9 KHN ± 0.8) for the SHR teeth compared to the Wistar teeth (enamel: 328.7 KHN ± 3.3 and dentin: 67.1 KHN ± 1.0). These results suggest that the SHR offspring are more susceptible to development of pathologies impairing oral health, once they presented lesser flow and salivary protein concentration and lower dental mineralization.

The long-term administration of calcineurin inhibitors decreases antioxidant enzyme activity in the rat parotid and submandibular salivary glands

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)