Chronic Central Nervous System MC3/4R Blockade Attenuates Hypertension Induced by Nitric Oxide Synthase Inhibition but Not by Angiotensin II Infusion
| Autor: | Shereen Hamza, Alexandre A. da Silva, Jussara M. do Carmo, John H. Dubinion, Kasra Mokhtarpouriani, John E. Hall, Mirian Bassi |
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| Rok vydání: | 2015 |
| Předmět: |
Central Nervous System
Male medicine.medical_specialty medicine.medical_treatment Blood Pressure Article Rats Sprague-Dawley Internal medicine Heart rate Internal Medicine medicine Animals Enzyme Inhibitors Infusions Intravenous Saline biology business.industry Angiotensin II Antagonist Rats Blockade Nitric oxide synthase Disease Models Animal medicine.anatomical_structure Blood pressure Endocrinology Ventricle Hypertension biology.protein Receptor Melanocortin Type 4 Nitric Oxide Synthase business Receptor Melanocortin Type 3 |
| Zdroj: | Hypertension. 65:171-177 |
| ISSN: | 1524-4563 0194-911X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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