Reduced renal vascular resistance in response to verapamil during gradated ureter obstruction in pigs

Unilateral ureteral obstruction (UUO) is associated with reductions in ipsilateral renal blood flow (RBF) and glomerular filtration rate (GFR) caused by an active preglomerular vasoconstriction, where angiotensin II (ANGII) may be an important mediator. Calcium-channel blockers preferentially dilate preglomerular vessels and abolish the vasoconstrictor actions of ANGII in preglomerular arterioles of the hydronephrotic rat kidney. In this study, we, therefore, examined the effects of the calcium-channel blocker verapamil (3.65 microg/kg per minute i.v.) on RBF, GFR and renal vascular resistance (RVR) in our pig model with UUO, where ultrasonic flow probes are mounted on each renal artery and catheters placed in the abdominal aorta and both renal veins. Verapamil treatment was associated with a 34% reduction in ipsilateral RBF (from 182.6 +/- 20.5 ml/min to 120.6 +/- 12.2 ml/min, P < 0.001), which was similar to the 27% reduction in ipsilateral RBF in controls (from 194.6 +/- 13.1 ml/min to 140.6 +/- 15.2 ml/min, P < 0.001). Ipsilateral GFR was reduced by 70% in the verapamil-treated pigs (from 29.0 +/- 2.6 to 8.5 +/- 0.9 ml/min, P < 0.001) and by 73% in control animals (from 29.2 +/- 3.1 to 7.6 +/- 2.1 ml/min, p < 0.001). However, the increase in RVR was significantly attenuated in the verapamil-treated pigs. Ipsilateral RVR increased by 19% in the verapamil-treated pigs (from 0.585 +/- 0.076 to 0.726 +/- 0.081 mmHg/min/ml, P < 0.05) compared with a 34% increase in control pigs (from 0.560 +/- 0.056 to 0.854 +/- 0.091 mmHg/min per milliliter, P<0.001), suggesting that an intact calcium-channel may be important for the increase in renal vascular resistance during unilateral ureter obstruction. In conclusion, the present study shows that verapamil is able to modulate the increase in renal vascular resistance in response to increased pelvic pressure.