Treatment with
dopamine receptor agonists has been shown to induce centrally mediated effects on cardiovascular regulation. We have investigated the effect on blood pressure and heart rate of stimulating the release of endogenous
dopamine in the brain from the mesolimbic/mesocortical (
A10) dopaminergic system of conscious Sprague-Dawley rats. Stimulation of the region of origin of the
A10 dopaminergic system, the ventral tegmental area (VTA), with local micro-injection of the
substance P analogue
DiMe-C7, produced a dose-dependent increase in blood pressure and heart rate. The injection of 10 nmol of
DiMe-C7 produced a maximum increase in blood pressure of 15-20 mmHg
at 10 min following administration and a maximum
tachycardia of 70-80 B/min. Intravenous pretreatment with the
dopamine D-1 receptor antagonist
SCH 23390 (0.1 mg/kg) or the
dopamine D-2 receptor antagonist
raclopride (0.5 mg/kg) markedly inhibited the pressor response and revealed a
bradycardia. Furthermore, the pressor response and
tachycardia were completely blocked by pretreatment with the
vasopressin V-1 receptor antagonist, Pmp1,O-Me-Tyr2-[Arg8]
vasopressin (10 micrograms/kg). Pretreatment with the
ganglion blocker,
pentolinium (10 mg/kg), had little effect on the blood pressure response, however it attenuated the
tachycardia. Micro-injection of 10 nmol of
DiMe-C7 into a region 2 mm dorsal to the VTA had little effect on blood pressure yet produced a marked
bradycardia. The administration of
DiMe-C7 into the region of origin of the nigrostriatal A9 dopaminergic system, the substantia nigra, produced a slight but significant increase in blood pressure with little effect on heart rate. Intracerebroventricular administration of
DiMe-C7 also produced a pressor response with a more pronounced
tachycardia. The blood pressure responses produced by intranigral or i.c.v. injection of
DiMe-C7 were not inhibited by pretreating the rats with
raclopride. These results suggest an involvement of the mesolimbic
A10 dopaminergic system in the regulation of blood pressure and heart rate through the activation of
dopamine D-1 and D-2 receptors and
vasopressin release.