Diltiazem increases renal prostacyclin.
We sought to determine whether the specific renal vasodilator effect of low dose diltiazem (D) was mediated by increased renal prostacyclin (PGI2) synthesis. Groups of 7-9 Sprague-Dawley rats were fitted with an indwelling transabdominal bladder cannula. Cannulae were placed in the jugular and femoral veins and the carotid artery and the rats allowed to recover for 24 h. Angiotensin II (AII) was infused intravenously at a rate (10 ng/kg/min) which increased mean arterial pressure (MAP) by 5-10%. After 30 min D(1 mg/kg and 2 micrograms/kg/min), D plus indomethacin (IND) (2 mg/kg and 33 micrograms/kg/min), IND plus vehicle or vehicle alone were added to AII. AII increased urinary 6-keto-prostaglandinF1 alpha (6-ketoPGF1 alpha) excretion from 1.36 +/- 0.12 to 1.86 +/- 0.20 ng/30 min (p less than 0.05) and D increased it further to 3.19 +/- 0.39 (p less than 0.05). Renal plasma flow (RPF) was estimated by 14C-PAH clearance (CPAH). Urinary excretion of 6-ketoPGF1 alpha was increased with AII indicating increased renal PGI2 synthesis. This increase in PGI2 was unable to prevent a reduction in RPF. D administration further increased the excretion of 6-ketoPGF1 alpha and reversed AII-induced renal vasoconstriction. IND augmented the AII response and prevented the effect of D, suggesting the renal vasodilator effect of D is, at least in part, PGI2-mediated. This mechanism may help maintain renal blood flow under conditions of vasoconstrictor stress.
Wilson
T W
TW
Departments of Pharmacology, University of Saskatchewan, Saskatoon.
Sharif
M N
MN
Kaushal
R D
RD
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004110:Diltiazem / Q000494:pharmacology*; D011464:Epoprostenol / Q000096:biosynthesis*; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D010130:p-Aminohippuric Acid / Q000378:metabolism
D000804:Angiotensin II; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D004110:Diltiazem; D007213:Indomethacin; D010130:p-Aminohippuric Acid