Effects of intrinsic prostaglandins on the spontaneous contractile and electrical activity of the proximal renal pelvis of the guinea-pig

Abstract

1. The effects of blocking prostaglandin biosynthesis with indomethacin on the spontaneous electrical and contractile activity recorded in smooth muscle strips of the guinea-pig renal pelvis were examined using standard tension and membrane potential recording techniques. 2. Circumferentially cut strips of proximal renal pelvis contracted more frequently (4.5 +/- 0.2 min-1) than strips cut from the mid region (1.3 +/- 0.2; P < 0.05, n = 5) of the renal pelvis. 3. Indomethacin (1 nM-10 microM) reduced the amplitude and frequency of the contractions of the renal pelvis in a concentration- and time-dependent manner. Contractions were completely abolished in the presence of 30 microM indomethacin. 4. After indomethacin blockade, activation of prostaglandin F2 alpha (PGF2 alpha) receptors with dinoprost (1-100 nM) restored the amplitude and frequency of the spontaneous contractions of renal pelvis. Higher concentrations of dinoprost (> 100 nM-3 microM) increased the contraction amplitude of the proximal and mid renal pelvis 1.9 and 1.6 times respectively. The contraction frequency of the mid renal pelvis, but not the proximal pelvis, was also raised above its pre-indomethacin frequency. 5. The spontaneous electrical activity recorded in proximal strips of the renal pelvis was designated to come from three cell types: (i), pacemaker cells (10% of cells recorded), with simple action potentials comprising relatively slow rising and repolarizing phases triggered on top of a slowly-developing pre-potential; (ii), driven cells (75% of cells), with complex action potentials comprising a rapid initial spike, followed by a period of membrane oscillation and a plateau of 0.2-2 s duration; and (iii), intermediate cells (15%) which fired action potentials with an initial rapid and a long plateau phase. 6. Indomethacin (10-30 micro M) decreased the amplitude and frequency of the action potentials recorded in driven and intermediate cells. The membrane potential of these cells also depolarized 5mV to-51.2 +/-2.6mV (n=5).7. Dinoprost (300 nM-1.5 micro M) increased the rate of action potential discharge, without affecting the membrane potential of driven cells previously exposed to indomethacin (30 micro M).8. These data suggest that the endogenous release of prostaglandins is necessary for the in vitro spontaneous contractile activity recorded in the guinea-pig renal pelvis. Blockade of the synthesis of these prostaglandins appears either to modify the ability of the driven regions of the renal pelvis to fire action potentials or to reduce the coupling of these driven regions to their pacemaker cells.