Central GABAergic control of cardiac function in different hypertrophy models

Cardiac hypertrophy is the clinical stage that precedes failure, whose pathophysiology relies on peripheral and central mechanisms. To evaluate whether pressure overload and/or cardiac β-adrenergic stimulation are the variables potentially linked to central GABAergic changes, we systematically compared different models of cardiac hypertrophy. Wistar rats (WT, >12 weeks of age) were instrumented for aortic coarctation (COA 30 days) or chronic beta-adrenergic stimulation with isoproterenol (ISO 1 mg/kg/day for 7 days), besides using spontaneously hypertensive (SHR, 14 weeks of age). Echocardiography confirmed hypertrophy in SHR, ISO and COA, with greater diastolic and systolic dysfunctions found in SHR. The inotropic performance of the ISO group was poorly influenced by afterload. In anesthetized rats, we recorded arterial and ventricular pressures before and after intracerebroventricular injection of GABA (200 nmol/2 μL), followed (20 min later) by the inhibitor of glutamate decarboxylase enzyme (GAD65/67), L-allylglycine (LAG - 87 nmol/2 μL). Brains were removed to assess gene and protein expression of the vesicular GABA transporter (VGAT), GAD65/67, and GABA receptor subtypes A (GABAA) and B (GABAB) in the hypothalamus and medulla. GABA reduced pressure and contractility in WT, SHR, ISO and COA groups without affecting chronotropy, while LAG increased chronotropy and inotropy only in ISO. While GAD65/67 and VGAT protein expression remained unchanged, GABAA levels were higher in the hypothalamus of SHR and GABAB were lower in SHR and COA medullary samples. Gene expressions of GABAA, GABAB, GAD65 and VGAT were higher in SHR hypothalamic samples. In conclusion, SHR is the hypertrophy model displaying the greater echocardiographic morphofunctional changes and presenting prominent alterations in hypothalamic and medullary GABAergic components.