Effects of ketanserin and DOI on spontaneous and 5‐HT‐evoked peristalsis of the pig ureter in vivo

Abstract

1 The in¯uence of 5-hydroxytryptamine (5-HT) receptor agonists and antagonists on the ureter motility was investigated in vivo on intact ureters of anaesthetized pigs. Drugs were administered intravenously or topically. 2 5-HT induced a dose-dependent increase in the frequency of ureter contractions in anaesthetized pigs when given intravenously (0.0001 ± 1 mg kg 71 ; ED 50 0.066 mg kg 71 ) or topically (0.001 ± 1 mg ml 71 ; EC 50 0.043 mg ml 71 ). Signi®cant increases in heart rate and blood pressure were observed when the drug was given intravenously but not topically. 3 The 5-HT 2A agonist, DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) increased the frequency of ureteral contractions in a dose-dependent manner (1 ± 300 mg kg 71 i.v.). Calculation of ED 50 indicated this compound to be about 1.5 times more potent with an e cacy of 23% compared to 5-HT. 4 The 5-HT 2A/2C antagonist, ketanserin (0.5 mg kg 71 ) and the 5-HT 2C antagonist, methysergide (1 mg kg 71 ) antagonized the 5-HT-induced ureter peristalsis when given intravenously. Contraction amplitude, blood pressure and heart rate were not a ected by the antagonists. 5 Intravenous (0.0001 ± 1 mg kg 71 ) and topical (0.0001 ± 1 mg ml 71 ) ketanserin signi®cantly decreased the frequency of spontaneous ureteral contractions to about 30% of controls, which could be partly reversed by 5-HT (0.3 mg kg 71 i.v.). The contraction amplitude, contractions of the contralateral, saline perfused ureter, heart rate and mean arterial blood pressure were not a ected. 6 Thus, contractility of porcine ureter is mediated by 5-HT 2 receptors. Their antagonists ketanserin and methysergide seem to be promising drugs for treatment of acute ureteric colic or in preparing the ureter for ureteroscopy.

Physiology and Pharmacology of the Human Ureter: Basis for Current and Future Treatments

“…5-HT 2 receptor antagonists (ketanserin and methysergide) antagonized the 5-HT-induced ureter peristalsis and decreased the frequency of spontaneous ureteral contractions in the pig and were suggested as being promising drugs for the management of ureteral colic [64] .…”

First Prize: Pharmacologic Manipulation of the Porcine Ureter: Acute Impact of Topical Drugs on Ureteral Diameter and Peristaltic Activity

“…12,13 To date, the in-vitro models described have utilized muscle baths to evaluate ureteral physiology. 14,[16][17][18] An interesting approach to the evaluation of ureteral muscle tone has been described by Miyatake and associates, 19 who described a model in which the force required to pull a glass bead through short piece of rabbit ureter was measured before and after application of pharmacologic agents. In this model, less force was required to pull the bead through the ureter after application of isoproterenol compared with a control ureter.…”

“…Both Danuser and associates 16 and Hauser and colleagues 17 showed that topical phenylephrine administration within the ureter in an anesthetized pig model produces a local effect on the ureter without the systemic side effects seen when the same drug is given intravenously. These groups used a 6F dual-lumen catheter placed through the renal pelvis and into the ureter.…”

Verapamil Inhibits the Pelvic Pressure Increase Corresponding to Flow Perfusion in the Porcine Percutaneous Renal Puncture Model

“…Ureteral access sheath also can provide protection against elevated renal pressures during routine ureteroscopic stone surgery [23]. In addition, some documents reported that some β-receptor agonist can cause relaxation of the upper urinary tract and reduce the pelvic pressure, such as β2-agonists and β3-agonists [6,9,11,12,13,14,15,18,19,24,25]. …”

“…Major experimental studies on modulating the smooth muscles in the ureter and pelvis in order to reduce pelvic pressure have been carried out in vitro and in vivo. Various pharmacological agents have shown great potential for lowering pelvic pressure, such as isoproterenol, terbutaline, norepinephrine, prostaglandin synthetase inhibitors and adrenaline [6,8,9,10,11,12,13,14,15]. In addition, a great deal of evidence has demonstrated that calcium channel blockers (CCBs) are capable of relaxing the smooth muscle of the ureter and pelvis as well as relieving ureteral colic [16,17,18,19].…”