Evidence for endothelin involvement in the response to high salt.
Recent evidence suggests that endothelin-1 (ET-1), perhaps through the ET(B) receptor, may participate in blood pressure regulation through the control of sodium excretion. Mean arterial pressure (MAP) was continuously measured via telemetry implants in male Sprague-Dawley rats. After 1 wk of baseline measurements, rats were given either high (10%) or low (0.08%) NaCl in chow for the remainder of the experiment (n = 5 in each group). MAP was significantly increased in rats on a high-salt diet (115 +/- 2 mmHg) compared with rats on the low-salt diet (103 +/- 2 mmHg; P < 0.05). All rats were then treated with the ET(B) receptor antagonist A-192621 mixed with the food and adjusted daily to ensure a dose of 30 mg x kg(-1) x day(-1). ET(B) blockade produced an increase in MAP within a few hours of treatment and was significantly higher in rats on the high-salt diet over a 1-wk period (170 +/- 3 vs. 115 +/- 3 mmHg, P < 0.01). To determine whether the increase in MAP during A-192621 treatment was due to increased ET(A) receptor activation, all rats were then given the ET(A)-selective antagonist ABT-627 in the drinking water while a low-salt/high-salt diet and ET(B) blockade were continued. ABT-627 decreased MAP within a few hours in rats on either the high-salt (113 +/- 3 mmHg) or low-salt (101 +/- 3 mmHg) diet. These results support the hypothesis that endothelin, through the ET(B) receptor, participates in blood pressure regulation in the response to salt loading.
Pollock
D M
DM
Vascular Biology Center, Department of Surgery, Medical College of Georgia, Augusta, Georgia 30912-2500, USA. dpollock@mail.mcg.edu
Pollock
J S
JS
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000378:metabolism* / Q000652:urine; D006339:Heart Rate / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D044023:Receptor, Endothelin B; D012965:Sodium Chloride / Q000008:administration & dosage; D012982:Sodium, Dietary / Q000008:administration & dosage*; D013686:Telemetry; D013997:Time Factors
C120508:A 192621; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D011759:Pyrrolidines; D044023:Receptor, Endothelin B; D012982:Sodium, Dietary; D012965:Sodium Chloride