AJP - Renal Physiology, Vol 250, Issue 2 197-F202, Copyright © 1986 by American Physiological Society
Role of the renal kinin-prostaglandin system in diltiazem-induced natriuresis
M. Seino, K. Abe, N. Nushiro, K. Omata, K. Sato, K. Tsunoda and K. Yoshinaga
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.
