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Exogenous diacylglycerol restores arteriolar myogenic constriction following candesartan (664.10)
Author(s) -
Hong Kwangseok,
Meininger Gerald,
Hill Michael
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.664.10
Subject(s) - candesartan , vasoconstriction , diacylglycerol kinase , endocrinology , medicine , chemistry , angiotensin ii , agonist , vascular smooth muscle , receptor , signal transduction , protein kinase c , smooth muscle , biochemistry
Growing evidence supports the G q/11 protein‐coupled angiotensin II type I receptor (AT 1 R) acting as a mechanosensor and contributing to pressure‐induced vasoconstriction of small arteries. While mechanical activation of the AT 1 R does not involve its classical agonist, angiotensin II, the exact signaling mechanisms underlying this mode of activation are yet to be delineated. Our recent studies have shown that pressure‐induced changes in global smooth muscle [Ca 2+ ] I are similar in the presence or absence of the AT 1 R inverse agonist, candesartan, implicating involvement of other second messenger‐mediated pathways. The aim of the present study was to further consider the generation of second messengers in response to AT 1 R activation and their role in myogenic vasoconstriction. Specifically, the diacylglycerol analog 1‐oleoyl‐2‐acetyl‐sn‐glycerol (OAG) was applied to isolated and pressurized rat cremaster arterioles in the presence and absence of candesartan. In the absence of candesartan OAG appeared to potentiate pressure‐induced vasoconstriction (e.g. control vs. OAG 10 µM; 44.2 ± 1.2 vs. 40.2 ± 1.5 µm). Candesartan (10 µM) alone showed significant inhibitory effects on steady‐state myogenic tone (control vs. candesartan at 70 mmHg; 50.3 ± 3.8 vs. 76.7 ± 8.2 µm; p < .05). This inhibition of myogenic reactivity was reversed in the presence of exogenous OAG (control vs. OAG 10 µM + candesartan at intraluminal pressures over the range 50 ‒ 110 mmHg; p > .05). Collectively, the data are consistent with mechanical activation of the AT 1 R resulting in generation of diacylglycerol and vasoconstriction that may be related to PKC‐dependent Ca 2+ sensitization or actin polymerization for pressure‐induced vasoconstriction. Grant Funding Source : Supported by NIH HL 092241 (MAH), HL 095486 (GAM)