Effect of BQ-123, an endothelin antagonist, on renal hemodynamics, tubular function, vasoactive hormones, and blood pressure in healthy humans: a dose response study.
BACKGROUND
Endothelin contributes to the maintenance of vascular tonus in both the systemic circulation and in regional vascular beds. The purpose of the study was to measure the effect of the endothelin A antagonist BQ-123 on renal hemodynamics, tubular function, vasoactive hormones, and blood pressure (BP) in healthy men.


METHODS
In a randomized, placebo-controlled, double-blind dose-response study of 11 healthy men we measured the effect of BQ-123 on glomerular filtrations rate (GFR), renal plasma flow (RPF), fractional excretion of sodium (FENa), lithium clearance (CLi), BP, and plasma concentrations of renin (PRC), angiotensin II (Ang II), atrial and brain natriuretic peptides (ANP, BNP), and vasopressin (AVP). BQ-123 was infused intravenously at the rate of 0.1, 0.2, and 0.3 mg/kg for 1 h, and the effects were measured before, during, and after infusion.


RESULTS
The GFR and RPF were not significantly changed by BQ-123. The FENa was increased (20%, medium dose), and CLi was unchanged. Systolic BP remained constant, whereas diastolic BP decreased (-6.3%, medium dose), and pulse rate increased (7.1%, medium dose). BQ-123 increased both PRC (62%, medium dose) and Ang II (70%, medium dose). The changes in FENa, diastolic BP, pulse rate, and Ang II gradually increased up to medium dose, and in PRC up to high dose. The ANP, BNP, and AVP were practically unchanged by BQ-123.


CONCLUSIONS
Infusion of an endothelin A antagonist resulted in an increase in renal sodium excretion despite a stimulation of the renin-angiotensin system and a decrease in diastolic BP.
Pedersen
Erling B
EB
Department of Medical Research, Holstebro Hospital and Aarhus University, Holstebro, Denmark.
Thomsen
Ingrid M
IM
Fjordside
Lene Sloth
LS
D000293:Adolescent; D000328:Adult; D000804:Angiotensin II / Q000097:blood*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D003971:Diastole; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D065130:Endothelin A Receptor Antagonists; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology*; D012079:Renal Circulation / Q000187:drug effects*; D012083:Renin / Q000097:blood*; D012964:Sodium / Q000652:urine; D014655:Vascular Resistance / Q000187:drug effects
D000959:Antihypertensive Agents; D065130:Endothelin A Receptor Antagonists; D010456:Peptides, Cyclic; D000804:Angiotensin II; D012964:Sodium; D012083:Renin; C072247:cyclo(Trp-Asp-Pro-Val-Leu)