title: Chronic central nervous system MC3/4R blockade attenuates hypertension induced by nitric oxide synthase inhibition but not by angiotensin II infusion.
abstract: 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.
authors.affiliation: From the Department of Physiology and Biophysics, Mississippi Center for Obesity Research, Center of Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson. asilva@umc.edu.
authors.forename: Alexandre A
authors.initials: AA
authors.lastname: da Silva
authors.affiliation: From the Department of Physiology and Biophysics, Mississippi Center for Obesity Research, Center of Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson.
authors.forename: Jussara M
authors.initials: JM
authors.lastname: do Carmo
authors.affiliation: From the Department of Physiology and Biophysics, Mississippi Center for Obesity Research, Center of Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson.
authors.forename: John H
authors.initials: JH
authors.lastname: Dubinion
authors.affiliation: From the Department of Physiology and Biophysics, Mississippi Center for Obesity Research, Center of Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson.
authors.forename: Mirian
authors.initials: M
authors.lastname: Bassi
authors.affiliation: From the Department of Physiology and Biophysics, Mississippi Center for Obesity Research, Center of Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson.
authors.forename: Kasra
authors.initials: K
authors.lastname: Mokhtarpouriani
authors.affiliation: From the Department of Physiology and Biophysics, Mississippi Center for Obesity Research, Center of Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson.
authors.forename: Shereen M
authors.initials: SM
authors.lastname: Hamza
authors.affiliation: From the Department of Physiology and Biophysics, Mississippi Center for Obesity Research, Center of Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson.
authors.forename: John E
authors.initials: JE
authors.lastname: Hall
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D002490:Central Nervous System / Q000378:metabolism*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007262:Infusions, Intravenous; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044104:Receptor, Melanocortin, Type 3 / Q000037:antagonists & inhibitors*; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D000804:Angiotensin II; D019001:Nitric Oxide Synthase
keywords: CNS; blood pressure; food intake; heart rate