We determined cardiovascular and neurohormonal responses to intracerebroventricular administration of human cocaine- and amphetamine-regulated transcript (CART) peptide 55-102 in conscious rabbits. Intracerebroventricular injection of CART 55-102 elicited dose-related increases in mean arterial pressure and renal sympathetic nerve activity. Peak values of mean arterial pressure and renal sympathetic nerve activity induced by intracerebroventricular injection of 1 nmol of CART 55-102 (+5.0±2.6 mm Hg and +72.5±20.8%) were obtained 40 and 60 minutes after injection, respectively. Plasma epinephrine and glucose concentrations significantly increased 30 and 60 minutes after intracerebroventricular injection of CART 55-102 (control versus 60 minutes for epinephrine, 77.0±62.4 versus 1067.5±329.3 pg/mL, P<0.01; for glucose, 6.25±0.33 versus 11.57±0.93 mmol/L, P<0.01). Plasma norepinephrine concentrations also significantly increased at 30 minutes. Plasma insulin, vasopressin, and cortisol concentrations increased at 60 minutes but did not attain significant values. However, pretreatment with intravenous injection of pentolinium (5 mg/kg), a ganglion-blocking agent, eliminated these cardiovascular and neurohormonal responses. In contrast, intravenous injection of the same dosage of CART 55-102 (1 nmol) as that used in the intracerebroventricular experiment failed to cause any cardiovascular and renal sympathetic nerve responses. These results surest that intracerebroventricular human CART 55-102 acts in the central nervous system and activates sympathoadrenal outflow, which results in increases in arterial pressure and plasma glucose levels in conscious rabbits.
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