Chronic central nervous system MC3/4R blockade attenuates hypertension induced by nitric oxide synthase inhibition but not by angiotensin II infusion.
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 μg/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 μL/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 (≈40 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.
['da Silva|Alexandre A|AA|', 'do Carmo|Jussara M|JM|', 'Dubinion|John H|JH|', 'Bassi|Mirian|M|', 'Mokhtarpouriani|Kasra|K|', 'Hamza|Shereen M|SM|', 'Hall|John E|JE|']
D000804:Angiotensin II D000818:Animals D001794:Blood Pressure D002490:Central Nervous System D004195:Disease Models, Animal D004791:Enzyme Inhibitors D006973:Hypertension D007262:Infusions, Intravenous D008297:Male D019001:Nitric Oxide Synthase D051381:Rats D017207:Rats, Sprague-Dawley D044104:Receptor, Melanocortin, Type 3 D044105:Receptor, Melanocortin, Type 4
blood pressure heart rate food intake CNS