Contribution of endothelin A receptors in endothelin 1-dependent natriuresis in female rats.
Renal medullary endothelin B receptors contribute to blood pressure regulation by facilitating salt excretion. Premenopausal females have relatively less hypertension than males; therefore, we examined whether there is a sex difference in the natriuretic response to renal medullary infusion of endothelin peptides in the rat. All of the experiments were conducted in anesthetized wild-type (wt) or endothelin B-deficient (sl/sl) rats. Infusion of endothelin 1 (ET-1) significantly increased sodium excretion (U(Na)V) in female, but not male, wt rats (Delta U(Na)V: 0.41+/-0.07 versus -0.04+/-0.06 micromol/min, respectively). The endothelin B receptor agonist sarafotoxin 6c produced similar increases in U(Na)V in both male (Delta 0.58+/-0.15 micromol/min) and female (Delta 0.67+/-0.18 micromol/min) wt rats. Surprisingly, ET-1 markedly increased U(Na)V in female (Delta 0.70+/-0.11 micromol/min) but not male sl/sl rats (Delta 0.00+/-0.05 micromol/min). ET-1 had no effect on medullary blood flow in females, although medullary blood flow was significantly reduced to a similar extent in males of both strains. These results suggest that the lack of a natriuretic response to ET-1 in male rats is because of reductions in medullary blood flow. Treatment with ABT-627, an endothelin A receptor antagonist, or N(G)-propyl-L-arginine, an NO synthase 1 inhibitor, prevented the increase in U(Na)V observed in female rats. Gonadectomy eliminated the sex difference in the U(Na)V and medullary blood flow response to ET-1. These findings demonstrate that there is no sex difference in endothelin B-dependent natriuresis, and the endothelin A receptor contributes to ET-1-dependent natriuresis in female rats, an effect that requires NO synthase 1. These findings provide a possible mechanism for why premenopausal women are more resistant to salt-dependent hypertension.
Nakano
Daisuke
D
Vascular Biology Center, Medical College of Georgia, 1459 Laney Walker Blvd, Augusta, GA 30912, USA.
Pollock
David M
DM
D000818:Animals; D000077868:Atrasentan; D004195:Disease Models, Animal; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006973:Hypertension / Q000378:metabolism; D007679:Kidney Medulla / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D011922:Rats, Mutant Strains; D044022:Receptor, Endothelin A / Q000378:metabolism*; D044023:Receptor, Endothelin B / Q000235:genetics / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D012727:Sex Characteristics; D012964:Sodium / Q000652:urine
D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D011759:Pyrrolidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D012964:Sodium; D000077868:Atrasentan