Role of the renal kinin-prostaglandin system in diltiazem-induced natriuresis.
Intravenous infusion of the Ca2+ entry blocker diltiazem (10 micrograms . kg-1 . min-1 for 30 min) induced an increase in urinary excretion of sodium (UNaV) from 209 +/- 42 to 922 +/- 311 mueq without significant alterations in renal hemodynamics in anesthetized rabbits. Urinary excretion of kinin (UkinV) and prostaglandin E (UPGEV) were also increased by diltiazem, from 14.3 +/- 2.5 to 25.9 +/- 4.8 ng and 1.33 +/- 0.20 to 2.44 +/- 0.34 ng, respectively. Moreover, there was a significant correlation between UkinV and UNaV (r = 0.81, P less than 0.05). A significant relationship between UPGEV and UNaV (r = 0.83, P less than 0.05) was also observed. However, no correlation between urinary excretion of kallikrein (UkallV) and UNaV was found after infusion of diltiazem. Further, to examine a possible contribution of renal kinins and prostaglandins in diltiazem-induced natriuresis, aprotinin (50,000 KIU/kg bolus + 1,000 KIU . kg-1 . min-1 infusion) and indomethacin (8 mg/kg) were used. Aprotinin pretreatment attenuated diltiazem-induced natriuresis, accompanied by suppression of UkallV, UkinV, and UPGEV. However, indomethacin pretreatment did not affect this drug-induced natriuresis, although UPGEV was significantly decreased. Furthermore, under the indomethacin pretreatment, a significant increase in UkinV was produced by diltiazem. These results suggest that renal kinins rather than renal prostaglandin E, at least in part, play a role in diltiazem-induced natriuresis.
Seino
M
M
Abe
K
K
Nushiro
N
N
Omata
K
K
Sato
K
K
Tsunoda
K
K
Yoshinaga
K
K
D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007610:Kallikreins / Q000652:urine; D007668:Kidney / Q000098:blood supply / Q000502:physiology*; D007705:Kinins / Q000502:physiology* / Q000652:urine; D009318:Natriuresis / Q000187:drug effects*; D011453:Prostaglandins / Q000502:physiology*; D011458:Prostaglandins E / Q000652:urine; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D001552:Benzazepines; D007705:Kinins; D011453:Prostaglandins; D011458:Prostaglandins E; D007611:Aprotinin; D007610:Kallikreins; D004110:Diltiazem; D007213:Indomethacin