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S6c‐induced hypertension is largely mediated through direct venoconstriction in female rats
Author(s) -
Li Melissa Wei,
Gariepy Cheryl E,
Fink Gregory Dale
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.21.6.a897-c
The endothelin ETB receptor (ETBR) agonist sarafotoxin 6c (S6c) causes sustained hypertension in rats. Because S6c produces natriuresis and relaxation of most arteries, but constricts most veins, we’ve proposed that S6c‐induced hypertension is due to venoconstriction. However, S6c also activates ETBRs in sympathetic ganglia to increase superoxide formation. This could increase sympathetic activity and blood pressure. The “rescued” ETBR‐deficient rat expresses functional ETBRs in sympathetic neurons, but not in blood vessels or renal tubules. Therefore, they were used to test where S6c acts to cause hypertension. Female ETBR‐deficient (−/−) and wild type (+/+) rats were instrumented with a radiotelemetry transmitter. After 3 control days, rats were given tempol (an antioxidant, 1 mmol/L in drinking water) for 3 days. S6c was then infused continuously (30 pmol/kg/min, sc) for 7 days. After 5 days of S6c‐infusion, tempol was removed. Following S6c infusion, rats were allowed a 4‐day recovery. Mean arterial pressure (MAP) was significantly higher in −/− than in +/+ rats (132 ± 3 vs 101 ± 3 mmHg) during the control period. S6c infusion increased MAP by 37 ± 2 mmHg in +/+ rats but only 7 ± 2 mmHg in −/−. Tempol had no effect on resting MAP or the response to S6c. The data indicate that S6c‐induced hypertension is not sympathetically mediated and support an important contribution by ETBR on venous smooth muscle. (NIH P01HL70687)