Systemic But Not Central Nervous System Nitric Oxide Synthase Inhibition Exacerbates the Hypertensive Effects of Chronic Melanocortin-3/4 Receptor Activation

作者：do Carmo Jussara M^*; Bassi Mirian; da Silva Alexandre A; Hall John E

来源：Hypertension, 2011, 57(3): 428-434.

DOI：10.1161/HYPERTENSIONAHA.110.163931

• blood pressure
• central nervous system
• food intake
• melanocortin system

We examined whether systemic or central nervous system (CNS) inhibition of nitric oxide synthase exacerbates the cardiovascular responses of chronic CNS melanocortin 3/4 receptor activation. Sprague-Dawley rats implanted with telemetry probes, venous catheters, and intracerebroventricular (ICV) cannulae were divided in 3 groups. After control measurements, the NO synthase inhibitor L-NAME was infused (10 mu g/kg/min intravenous) for 17 days and, starting on day 7 of L-NAME infusion, the melanocortin 3/4 receptor agonist melanotan II (MTII; 10 ng/hr; group 1) or saline vehicle (group 2) was infused ICV for 10 days. A third group not treated with L-NAME also received MTII ICV. Melanocortin 3/4 receptor activation caused a greater increase in mean arterial pressure (MAP) and heart rate in rats treated with intravenous L-NAME (35 +/- 6 mm Hg and 56 +/- 8 bpm) than L-NAME plus vehicle or MTII alone (22 +/- 5 and 9 +/- 2 mm Hg, and 26 +/- 14 and 27 +/- 5 bpm), despite a 58% and 50% reduction in food intake during the first 6 days of MTII infusion. To test if the amplified pressor response to MTII after L-NAME was attributable to a reduction in nitric oxide availability in the brain, we also infused L-NAME directly into the CNS alone or in combination with MTII. ICV infusion of L-NAME plus MTII caused only approximate to 10 mm Hg increase in MAP with no change in heart rate, similar to the effects of ICV infusion of MTII alone, whereas ICV infusion of L-NAME alone had no effect on MAP. These results suggest that reduction in peripheral, but not CNS, nitric oxide production augments MAP sensitivity to CNS melanocortin 3/4 receptor activation. (Hypertension. 2011;57:428-434.)

• 出版日期2011-3