Objective To investigate the effect of partial bladder outlet obstruction on detrusor blood¯ow and oxygen tension (PdetO 2 ) in female pigs. Materials and methods Detrusor-layer oxygen tension and blood¯ow were measured using oxygen-sensitive electrode and radiolabelled microsphere techniques in ®ve female Large White pigs with a partial urethral obstruction and in ®ve sham-operated controls. The effects of chronic outlet obstruction on bladder weight, and cholinergic nerve density and distribution, are also described. Results In the obstructed bladders, blood¯ow and oxygen tension were, respectively, 54.9% and 74.3% of control values at low bladder volume, and 47.5% and 42.5% at cystometric capacity. Detrusor blood¯o w declined by 27.8% and 37.5% in the control and obstructed bladders, respectively, as a result of bladder ®lling, whilst PdetO 2 did not decrease in the controls, but fell by 42.7% in the obstructed bladders. Bladder weight increased whilst cholinergic nerve density decreased in the obstructed animals. Conclusion In pigs with chronic bladder outlet obstruction, blood¯ow and oxygen tension in the detrusor layer were lower than in control animals. In addition, increasing detrusor pressure during ®lling caused signi®cantly greater decreases in blood¯ow and oxygen tension in the obstructed than in the control bladders.
In anesthetized pigs with ultrasonic flow probes mounted on each renal artery and catheters placed in the abdominal aorta and both renal veins, renal blood flow (RBF), glomerular filtration rate (GFR) and filtration fraction (FF) were investigated during stepwise unilateral ureteral obstruction. Elevation of the ureteral pressure in steps of 10 mm Hg to a maximum of 80 mm Hg decreased ipsilateral RBF by 45 ± 3% from 300 ± 25 to 168 ± 20 ml/min (p < 0.01). Contralateral RBF did not change significantly. The mean arterial pressure was constant during the experimental procedures, suggesting that the decrease of RBF was due to a significant increase in ipsilateral renal vascular resistance. Concomitantly with these changes ipsilateral GFR was reduced by 75% from 40 ± 2 to 10 ± 3 ml/min. In the contralateral kidney, GFR was unchanged during the experiment. The renal extraction of 51Cr-EDTA equal to FF increased temporarily from 0.202 ± 0.013 at start to 0.239 ± 0.015 (p < 0.05) at 20 mm Hg in the ipsilateral kidney, whereafter it was dramatically reduced to 0.090 ± 0.024 at maximum pressure. In addition, renal tubular handling of salt and water in the contralateral kidney were investigated using the lithium clearance technique. No significant changes were found. In conclusion, the renal hemodynamic changes during ureteral obstruction are compatible with a predominant preglomerular vasoconstriction. The interrelationship between obstruction, high pressure and reduction in RBF and GFR is substantiated. Moreover, variation in the reactive mechanisms between species with different kidney activities is established.
The porcine urological system is similar anatomically and physiologically to that of humans. Swine have a true multirenculate, multipapillate kidney with a calyceal system like that of humans. The gross anatomic and histologic characteristics of the porcine and the human kidney are more similar than most other commonly used laboratory animals. The physiologic functions of the urinary system including urodynamic parameters are also similar to humans. Swine have been used extensively as models of urologic conditions in humans, most commonly in obstructive urologic syndromes. A large number of investigative procedures can be performed in one experiment both in acute and chronic models. Recently, a new technique of surgically induced antenatal lower urinary tract obstruction in swine has been developed.
Unilateral ureteral obstruction in pigs is associated with an enhanced, de novo generation of angiotensin II from the ipsilateral kidney. In order to further investigate the role of this system during unilateral ureter obstruction, the renal hemodynamic response to the non-peptide angiotensin II antagonist losartan was investigated. Danish land race pigs were operated on under general anesthesia. Catheters were placed in both renal veins by x-ray and ultrasonic flow probes were mounted on the renal arteries. Losartan (2 mg/kg/h) was administered intravenously to an experimental group ( n=9) continuously over 8 h of unilateral ureteral occlusion. This group was then compared to a matched control group which received only saline ( n=6). Ipsilateral pelvic pressure, renal blood flow using ultrasound transit time, glomerular filtration rate, mean arterial pressure and heart rate were measured. Renal handling of angiotensin II was examined by determining the renal extraction and secretion rates of immunoreactive angiotensin II. The anticipated reduction in ipsilateral renal blood flow after the onset of obstruction was attenuated in the losartan treated pigs, but the ipsilateral glomerular filtration rate was unaffected as compared with the controls. In the losartan group, the increase in renal vascular resistance was significantly reduced compared with un-treated controls (141+/-25% vs 217+/-24%, P<0.05). Plasma immunoreactive angiotensin II increased significantly from all three sample locations in both groups after the onset of obstruction, being more pronounced in the losartan treated group in which immunoreactive angiotensin II from the ipsilateral renal vein increased from 5.1+/-0.5 pmol/l to 41.6+/-19.6 pmol/l, P=0.027. In the controls immunoreactive angiotensin II increased from 2.7+/-0.3 pmol/l to 24.8+/-10.2 pmol/l. Furthermore, plasma aldosterone was significantly reduced after losartan administration (from 80.4 pmol/l to 36.0 pmol/l, P=0.005), indicating effective blockade of the angiotensin II type-1 receptor. The results from the present study suggest that continuous intravenous administration of losartan blocks the angiotensin II receptor mediated effects in the pig. Losartan is able to reduce ipsilateral vasoconstriction in the obstructed kidney during unilateral ureter obstruction supporting the view that angiotensin II is an important mediator of vasoconstriction during unilateral ureter obstruction in the pig model with acute unilateral occlusion of the ureter.
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.
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