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Chronic central nervous system MC3/4R activation exacerbates the cardiovascular responses to peripheral nitric oxide synthase inhibition
Author(s) -
Carmo Jussara M,
Bassi Mirian,
Silva Alexandre A,
Hall John E
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1051.1
Subject(s) - endocrinology , medicine , nitric oxide , blood pressure , nitric oxide synthase , sympathetic nervous system , heart rate , agonist , autonomic nervous system , central nervous system , chemistry , anesthesia , receptor
We examined if nitric oxide synthase inhibition exacerbates the cardiovascular responses of central nervous system (CNS) melanocortin‐3/4 receptor (MC3/4R) activation. Sprague‐Dawley rats implanted with telemetry device, venous catheter and intracerebroventricular (ICV) cannula were divided in 2 groups: After 5 days of control measurements, L‐NAME was infused (14 mg/kg/day, i.v.) for 17 days. Starting on day 7 of L‐NAME infusion, the MC3/4R agonist MTII (240 ng/day, n=7 – group 1), or vehicle (n=6 – group 2) was infused ICV for 10 days. L‐NAME + MTII caused a larger increase in blood pressure (BP: 110±3 to 183±3 mmHg) and heart rate (HR: 383±9 to 437±10 bpm) compared to L‐NAME + vehicle treatment (103±2 to 161±6 mmHg and 371±7 to 364±17 bpm). The increase in BP and HR in the L‐NAME + MTII group occurred despite a 60% reduction in food intake during the first 6 days of MTII infusion. MC3/4R activation also reduced glucose and insulin levels by ~30% and 35%. We then tested if the exacerbated pressor responses to combined L‐NAME + MTII treatment was due to a reduction in nitric oxide (NO) levels in the brain by infusing L‐NAME alone, or in combination with MTII, into the CNS. Central infusion of L‐NAME + MTII caused only ~10 mmHg increase in BP with no change in HR, whereas L‐NAME alone had no effect on BP. These results suggest that peripheral, but not central, reduction in NO production augments the sensitivity to CNS MC3/4R activation