RESUMO

The antihypertensive drugs moxonidine and clonidine are α2-adrenoceptor and imidazoline (I1) agonists. Previous results from our laboratory have shown that moxonidine can act in the commissural nucleus of the solitary tract (commNTS). In addition, some studies have shown that GABA or glutamate receptor blockade in the RVLM blunted the hypotension produced by these antihypertensive agents in spontaneously hypertensive rats. Therefore, in the present study we verify whether the cardiovascular and sympathetic effects produced by moxonidine in the commNTS are dependent on GABAergic or glutamatergic mechanisms. Mean arterial pressure (MAP) and splanchnic sympathetic nerve activity (sSNA) were recorded in urethane-anesthetized, and artificially-ventilated male Wistar rats (250-350 g). Injection of the GABAA antagonist bicuculline (25 pmol/50 nL) into the commNTS reduced the hypotension as well as the sympathoinhibition elicited by moxonidine. Prior injection of the glutamate receptor antagonist kynurenic acid (2.5 nmol/50 nL) into the commNTS was not effective in reducing the hypotension and sympathoinhibition elicited by moxonidine. Therefore, we conclude that the hypotensive and sympathoinhibitory effects elicited by microinjection of moxonidine into the commNTS are dependent on GABA receptors, but not ionotropic glutamate receptors.

Assuntos

Anti-Hipertensivos/farmacologia , Fenômenos Fisiológicos Cardiovasculares/efeitos dos fármacos , Imidazóis/farmacologia , Núcleo Solitário/efeitos dos fármacos , Ácido gama-Aminobutírico/metabolismo , Análise de Variância , Animais , Bicuculina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Receptores de GABA-A/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Ácido Cinurênico/farmacologia , Masculino , Ratos , Ratos Wistar , Nervos Esplâncnicos/efeitos dos fármacos , Nervos Esplâncnicos/fisiologia , Fatores de Tempo

RESUMO

BACKGROUND: The literature did not evidence yet with which age spontaneously hypertensive rats (SHR) start to present baroreflex reduction. We endeavored to evaluate the baroreflex function in eight-week-old SHR. METHODS: Male Wistar Kyoto (WKY) normotensive rats and SHR aged eight weeks were studied. Baroreflex was calculated as the variation of heart rate (HR) divided by the mean arterial pressure (MAP) variation (DeltaHR/DeltaMAP) tested with a depressor dose of sodium nitroprusside (SNP, 50 microg/kg) and with a pressor dose of phenylephrine (PHE, 8 microg/kg) in the right femoral venous approach through an inserted cannula in the animals. Significant differences for p < 0.05. RESULTS: Baseline MAP (p < 0.0001) and HR (p = 0.0028) was higher in SHR. Bradycardic peak was attenuated in SHR (p < 0.0001), baroreflex gain tested with PHE was also reduced in the SHR group (p = 0.0012). PHE-induced increase in MAP was increased in WKY compared to SHR (p = 0.039). Bradycardic reflex responses to intravenous PHE was decreased in SHR (p < 0.0001). CONCLUSION: Eight weeks old SHR already presents impairment of the parasympathetic component of baroreflex.