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Overexpression of Na/Ca exchanger‐1 (NCX1) in vascular smooth muscle leads to elevated basal blood pressure and increased responses to Angiotensin II
Author(s) -
Chen Ling,
Li Meng,
Wier W. Gil,
Wang Jingyu,
Zhang Jin
Publication year - 2012
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.26.1_supplement.872.2
Subject(s) - medicine , endocrinology , basal (medicine) , angiotensin ii , vasoconstriction , chemistry , blood pressure , sodium calcium exchanger , vascular smooth muscle , renin–angiotensin system , calcium , smooth muscle , insulin
Ca 2+ entry via vascular smooth muscle (VSM) Na + /Ca 2+ exchanger type‐1 (NCX1) was reported to trigger salt‐dependent hypertension. Here, we investigated whether VSM‐specific NCX1 overexpression modifies basal blood pressure (BP) and Angiotensin II (ANG)‐induced BP response. Adult wild type (WT) and age‐matched transgenic mice that express ~7 fold higher VSM NCX1 protein (NCX TG) were used. Under 1.5% isoflurane anesthesia, BP was continuously recorded with a Millar catheter via right carotid artery. NCX TG mice had significantly higher baseline BP compared to WT controls (95 ± 9 vs 81 ± 2 mm Hg, P < 0.05, n = 6 and 8). ANG injection (30 ng/kg in 50 μl saline, 10s, i.v.) caused a significantly greater BP elevation in NCX TG than in WT mice (33 ± 3% vs 20 ± 3%, P < 0.05; n = 3 and 6). A higher dosage of ANG (300 ng/kg) resulted in greater BP elevation in both groups, but no significant difference was observed between genotypes (38 ± 4% vs 52 ± 6%; P = 0.076). Thus, VSM NCX1 overexpression increases basal BP and exaggerates acute BP response to ANG. The elevated basal BP in NCX TG mice indicates that arterial NCX1 normally provides net Ca influx in the basal state. In this case, both cytosolic and sarcoplasmic reticulum [Ca 2+ ] would be expected to be elevated, providing both increased vascular tone in the basal state and increased vasoconstriction in response to G‐protein coupled receptor agonists, such as ANG. (Supported by NHLBI and AHA).