Chronic Central Nervous System MC3/4R Blockade Attenuates Hypertension Induced by Nitric Oxide Synthase Inhibition but Not by Angiotensin II Infusion

被引:15
作者
da Silva, Alexandre A. [1 ]
do Carmo, Jussara M. [1 ]
Dubinion, John H. [1 ]
Bassi, Mirian [1 ]
Mokhtarpouriani, Kasra [1 ]
Hamza, Shereen M. [1 ]
Hall, John E. [1 ]
机构
[1] Univ Mississippi, Dept Physiol & Biophys, Mississippi Ctr Obes Res, Ctr Excellence Cardiovasc Renal Res,Med Ctr, Jackson, MS 39216 USA
关键词
blood pressure; CNS; food intake; heart rate; MELANOCORTIN SYSTEM; ARTERIAL-PRESSURE; BLOOD-PRESSURE; OBESITY; RECEPTORS; LEPTIN; RATS; ACTIVATION; RESPONSES; PATHWAYS;
D O I
10.1161/HYPERTENSIONAHA.114.03999
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
We examined whether central melanocortin 3 and 4 receptor (MC3/4R) blockade attenuates the blood pressure (BP) responses to chronic L-NAME or angiotensin II (Ang II) infusion in Sprague-Dawley rats implanted with telemetry transmitters, venous catheters, and intracerebroventricular cannula into the lateral ventricle. After 5 days of control measurements, L-NAME (10 mu g/kg/min IV, groups 1 and 2) or Ang II (10 ng/kg/min IV, groups 3 and 4) were infused for 24 days, and starting on day 7 of L-NAME or Ang II infusion, the MC3/4R antagonist SHU-9119 (24 nmol/d, n=6/group; groups 1 and 3) or vehicle (saline 0.5 mu L/h, n=6/group; groups 2 and 4) was infused intracerebroventricularly for 10 days. A control normotensive group also received SHU-9119 for 10 days (n=5). L-NAME and Ang II increased BP by 40+/-3 and 56+/-5 mm Hg, respectively, although heart rate was slightly reduced. MC3/4R blockade doubled food intake and reduced heart rate (approximate to 40 to approximate to 50 bpm) in all groups. MC3/4R blockade caused only a small reduction in BP in normotensive group (4 mm Hg) and no change in rats receiving Ang II, although markedly reducing BP by 21+/-4 mm Hg in L-NAME-treated rats. After SHU-9119 infusion was stopped, food intake, heart rate, and BP gradually returned to values observed before SHU-9119 infusion was started. Ganglionic blockade at the end of L-NAME or Ang II infusion caused similar BP reduction in both groups. These results suggest that the brain MC3/4R contributes, at least in part, to the hypertension induced by chronic L-NAME infusion but not by Ang II.
引用
收藏
页码:171 / 177
页数:7
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