Endothelin-1-induced renal vasoconstriction is blunted by enalaprilat and enhanced by EDRF antagonist in awake normotensive rats.
We attempt to elucidate the putative indirect mechanisms by which endothelin-1 affects mean blood pressure and renal blood flow in normotensive awake rats. Endothelin-1 (700 pg/kg, i.v.) induced a short-lasting decrease followed by a prolonged increase in mean blood pressure (from 113 +/- 4 to 92 +/- 4 mmHg at 30 sec, 132 +/- 7 mmHg at 10 min, and 129 +/- 6 mmHg at 30 min, p less than 0.01), and caused a profound and long-lasting fall in renal blood flow as measured by Doppler flowmeter technique (from 2.87 +/- 0.29 to 1.40 +/- 0.37 kHz at 30 sec, 1.77 +/- 0.32 kHz at 10 min and 2.10 +/- 0.45 kHz at 30 min, p less than 0.01). Neither the receptor antagonist of bradykinin D-Arg0-Hyp3-Thi5,8-DPhe7-bradykinin (30 micrograms/kg/min, i.v.) nor the antagonist of angiotensin II Sar1, Thr8-angiotensin II (4 micrograms/kg/min, i.v.) altered the changes in mean blood pressure and renal blood flow induced by endothelin-1. The antagonist of EDRF synthesis, NG-monomethyl-L-arginine (100 micrograms/kg/min, i.v.) enhanced the endothelin-1-induced increase in mean blood pressure (endothelin-1: 20 +/- 2 mmHg vs endothelin-1 + EDRF antagonist: 39 +/- 3 mmHg at 10 min, p less than 0.01) and decrease in renal blodo flow (endothelin-1: -40 +/- 4% vs endothelin-1 + EDRF antagonist: -73 +/- 3% at 10 min, p less than 0.01).2+ mediated by the blockade of angiotensin II formation.
Madeddu
P
P
Clinica Medica and Farmacologia, University of Sassari, Italy.
Anania
V
V
Parpaglia
P P
PP
Troffa
C
C
Pazzola
A
A
Soro
A
A
Manunta
P
P
Tonolo
G
G
Demontis
M P
MP
Varoni
M V
MV
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D015773:Enalaprilat / Q000494:pharmacology*; D016232:Endothelins / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D019323:omega-N-Methylarginine
D016232:Endothelins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D015773:Enalaprilat