Objective: 

Therapeutic/pathological reactions to hormones/drugs, esp. in urogenital tract, are well known, but not to toxicants. Summary of recent and earlier observations is given [1,2].

Methods: 

Isolated detrusor preparations of guinea-pig (GP) and rat urinary bladder in organ-bath with McEwen-solution (37°C): Influence of chlorophenols and pyrethroids (hydrophobe substances), i.e. pentachlorophenol/cypermethrin in physiological solution +0.1–1% ethanol, trichlorophenol/deltamethrin in physiological solution +0.1–1% acetone, on motor activity (isotonic recording) was investigated. Spontaneous phasic contractions (SPC-frequency:3.84±0.95/min, n=61) and contractions to neurogenic electrical-stimulation (CES:10&100Hz, 0.3ms-3s-3min) were recorded. Changes are given in % of initial values [2].

Results: 

1. GP-Detrusor: (a) SPC-amplitudes decreased stronger after pentachlorophenol (10.1±8.3%) than trichlorophenol (55.4±16.2%). (b) Pentachlorophenol/deltamethrin (100mM) inhibited CES-100Hz stronger (25.1±27.5%/9.7±3.8%) than trichlorophenol/cypermethrin (70.9±13.0%/74.7±3.6%). 2. Rat-detrusor: (a) Pentachlorophenol-effect (100mM) was stronger, i.e. abolished SPC-frequency (0.0±0.0%), than at GP-detrusor (55.7±33.9%), (b) also inhibition of rat CES-10Hz (5.6±5.5%) & 100 Hz (2.4±0.3%) was stronger than this of GP (21.3±10.4% & 25.1±27.5% resp.). 3. Varia: (a) Frequency of slow tonic contractions (STC:0.13±0.55/min, n=26) of GP-trigone decreased upto 50% after cypermethrin (10–100mM). (b) Contrary to this HgCl2 (1–10mM) had strong positive chrono-/inotropic effects.

Conclusions: 

Immediate pathophysiological vesical motor reactions could be high sensitive indicators for prophylaxis of functional disturbances (incontinence, overactive-bladder, etc.) - it is recommendable to proof human relevancy on surgical tissue. These toxicants could be also useful for physiological analysis (Cl.Bernard), e.g. role of mechanosenstitive ionic channels (Ca²⁺-activated K⁺) for SPC-STC: Pentachlorophenol & cypermethrin (1–100mM) transformed spikes into bursts/burst-plateaus in detrusor-myocytes, i.e. activates stretch channels. Differentiation of neurogenic and myogenic mechanisms needs further experiments [1–3].

References: [1] Haerlin et-al.: Basic&Clin.-Pharm.&Tox. 107:320/2010 (IUPHAR-Copenhagen); [2] Neu/Haerlin/Hofstetter et-al.: Urology 68/5A:78-79/2006 (SIU-Cape Town); Chin.J.Pathophysiol. 22/13 (Suppl.):228/2006 (Int.Soc.Pathophys.-Beijing); Eur.J.Physiol. 420:S393/1992, 419:124/1991; [3] Michailov/Neu/Welscher et-al.: British-J.Urol. 94:24-25&258-259/2004 (SIU-Honolulu); IUPS-Proc.(22): J.Physiol. Sci.59:249/2009 (Kyoto), (21):Faseb-J.19/4:A585/2005 (San-Diego), 17:529/1989 (Helsinki), 14:580/1980 (Budapest).