Blunted endogenous GABA-mediated inhibition in the hypothalamic paraventricular nucleus of rats with streptozotocin-induced diabetes
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The hypothalamic paraventricular nucleus (PVN) is involved in the regulation of sympathetic outflow and particularly affects the heart. This study sets out to determine the role of GABA of the paraventricular nucleus (PVN) in cardiovascular regulation in streptozotocin-induced diabetic rats. Pharmacological stimulation of glutamatergic receptors with DL-Homocysteic acid (200 mM in 100 nL) in the PVN region showed a significant depression in both mean arterial pressure (MAP) and heart rate (HR) of diabetic rats (Diabetic vs. non-diabetic: MAP 15.0 ± 1.5 vs. 35.8 ± 2.8 mmHg; HR 3.0 ± 2.0 vs. 30.0 ± 6.0 bpm, P < 0.05). Microinjection of bicuculline methiodide (1 mM in 100 nL), a GABAA receptor antagonist, produced an increase in baseline MAP and HR in both non-diabetic and diabetic rats. In the diabetic rats, bicuculline injection into the PVN reduced the pressor and HR responses (Diabetic vs. non-diabetic: MAP 6.2 ± 0.8 vs. 25.1 ± 2.2 mmHg; HR 1.8 ± 1.1 vs. 25.4 ± 6.2 bpm, P < 0.05). A microinjection of muscimol (2 mM in 100 nL), which is a GABAA receptor agonist, in the PVN elicited decreases in MAP and HR in both groups. The diabetic group showed a significantly blunted reduction in HR, but not MAP (Diabetic vs. non-diabetic: MAP −15.7 ± 4.0 vs. −25.0 ± 3.8 mmHg; HR −5.2 ± 2.1 vs. −39.1 ± 7.9 bpm). The blunted vasopressor and tachycardic responses to bicuculline microinjection in the diabetic rats are likely to result from decreased GABAergic inputs, attenuated release of endogenous GABA or alterations in GABAA receptors within the PVN.
KeywordsGABAA receptors Bicuculline methiodide Muscimol Paraventricular nucleus STZ-induced diabetic rats
This research was supported financially by Research University Grant (1001/PFARMASI/811053) from Universiti Sains Malaysia.
- 8.Dampney RAL, Tagawa T, Fontes MAP (2000) Evidence for a tonic glutamatergic input from the hypothalamic paraventricular nucleus to rostral VLM pressor neurons. FASEB J 14:A623Google Scholar
- 28.Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 2nd edn. Academic Press, San DiegoGoogle Scholar
- 31.Schann BD, Maeda CY, Timm HB, Medeiros S, Moraes RS, Ferlin E, Fernandes TG, Ribeiro JP, Schmid H, Irigoyen MC (1997) Time course of changes in heart rate and blood pressure variability in STZ-induced diabetic rats treated with insulin. Braz J Med Biol Res 30:1081–1086Google Scholar