Increased cardiovascular responsiveness to GABAergic stimulation in DOCA-salt hypertensive rats.

Cardiovascular responsiveness to intracerebroventricular (icv) administration of dopamine (50, 100 and 200 micrograms/kg), muscimol (1 and 2 micrograms), and ethanolamine-O-sulphate (EOS; 5, 10, 20 and 40 mumol) as well as GABA content in several brain areas were examined in rats, made diabetic by an intravenous (iv) injection of streptozotocin (STZ; 40 mg/Kg). Citrate buffer (pH 4.5) treated animals were used as controls. Experiments were carried out in conscious rats with chronically implanted icv cannulae and iv and intraarterial catheters, 1 and 3 weeks after STZ injection. Diabetic rats exhibited: 1) higher hyperglicaemia after 1 week than after 3 weeks; 2) normal mean arterial pressure (MAP) both after 1 and 3 weeks, and 3) bradycardia only after 3 weeks. Icv injections of muscimol, a GABA receptor agonist, and EOS, an inhibitor of GABA breakdown, caused a dose-dependent decrease in MAP and heart rate (HR), which was significantly higher than that elicited in control animals. GABA content was reduced in the hypothalamus (already after 1 week), and in the brainstem (but only after 3 weeks). No changes in GABA content were detected in other brain areas. Icv injection of dopamine elicited a dose dependent decrease in MAP and HR either in diabetic or in control rats, with no difference between groups. The results suggest that diabetes alters cerebral GABAergic control of arterial blood pressure and heart rate in the rat.