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Differential blood pressure response in normotensive rats and rats with angiotensin II‐dependent hypertension following systemic cannabinoid CB1 receptor blockade (1140.11)
Author(s) -
Schaich Chris,
Howlett Allyn,
Brosnihan K.,
Diz Debra
Publication year - 2014
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.28.1_supplement.1140.11
Subject(s) - blockade , medicine , blood pressure , endocrinology , renin–angiotensin system , endocannabinoid system , cannabinoid , angiotensin ii , receptor , cannabinoid receptor , cannabinoid receptor antagonist , antagonist , chemistry
Evidence for interactions between the endocannabinoid (ECS) and the renin‐angiotensin (RAS) systems in brain and vasculature is emerging. In transgenic (mRen2)27 rats, an angiotensin (Ang) II‐dependent model of hypertension involving excess sympathetic nervous system activity (SNS), acute systemic blockade of CB1 cannabinoid receptors by the CB1‐selective antagonist SR141716A (SR; 10 mg/kg orally; n = 5) significantly reduced systolic blood pressure (SBP) from 176 ± 3 mmHg baseline to 134 ± 3 mmHg after 90 min (P < 0.001). SBP showed evidence of recovery after 24 h but remained significantly reduced at 146 ± 5 mmHg (P < 0.01) compared to baseline. Plasma collected at 24 h showed no differences in levels of Ang II and Ang‐(1‐7) in the SR‐treated group compared to the vehicle (0.1% Tween‐80 in dH2O) group. Interestingly, oral SR treatment in normotensive Sprague‐Dawley control rats (n = 2) modestly increased SBP from a baseline of 120 ± 3 mmHg to 135 ± 2 mmHg after 90 min, suggesting blockade of the known vasodilator actions of the CB1 receptor. After 24 h, SBP recovered to 126 ± 4 mmHg. There was no effect of vehicle on SBP in either strain. These results indicate that CB1 receptor blockade in (mRen2)27 rats may disrupt the hypertension by interfering with the upregulated RAS‐dependent excess SNS activity in these animals, overcoming the blockade of the beneficial ECS effects in the vasculature. Grant Funding Source : Supported by NIH: P01‐HL051952 and R01‐DA03690

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