Response of Rabbit Detrusor Muscle to Total Extract and Major Alkaloids of Hydrastis canadensis P. Bolle,* M. F. Cometa, M. Palmery and P. Tucci Institute of Pharmacology and Pharmacognosy, University of Rome ‘La Sapienza’, P.le Aldo Moro 5, 00185 Rome, Italy Hydrastis canadensis L. (Ranunculaceae) is used in traditional medicine to treat numerous diseases, in- cluding bladder disorders and prostatitis. This study was designed to ascertain in bladder detrusor mus- cle the effects of an ethanol extract of the major alkaloids in Hydrastis canadensis. On rabbit bladder strips, the total extract of Hydrastis canadensis induced relaxation nearly comparable to the response evoked by isoproterenol (EC 50 ); propranolol partly blocked relaxation induced by the extract. Conver- sely, when the major alkaloids in Hydrastis canadensis (berberine, b-hydrastine, canadine and canada- line) were added to the bath separately at concentrations several times higher than those present in the extract, none of them induced relaxation. These findings suggest that the relaxing effect depends on com- ponents other than the tested alkaloids, that the extract induces relaxation only partly through b-adre- noreceptors and that other mechanisms must be involved. # 1998 John Wiley & Sons, Ltd. Phytother. Res. 12, S86–S88 (1998) Keywords: Hydrastis canadensis; benzylisoquinoline alkaloid pharmacology; rabbit detrusor strips; b-adrenoceptors. INTRODUCTION Hydrastis canadensis (Ranunculaceae) is a small per- ennial plant indigenous to eastern Canada and the USA. In popular medicine, extracts of rhizomes and roots are used to treat catarrhal conditions of the urogenital tract and to control uterine haemorrhage (Evans, 1989). A multi-ingredient preparation containing Hydrastis cana- densis is used in Australia to treat urinary bladder disorders and prostatitis (Reynolds, 1996). Hydrastis canadensis extract relaxes guinea-pig trachea and rat uterus (Cometa et al., 1998). This study was designed to ascertain whether Hydrastis canadensis extract and its major alkaloids berberine, b-hydrastine, canadine and canadaline had a muscle-relaxing activity also on bladder detrusor muscle. MATERIALS AND METHODS Tissue preparation. Male New Zealand rabbits weigh- ing about 2.7 kg were used. Animals were killed by a blow on the head and bled rapidly. A strip of detrusor muscle (about 2 mm wide and 6 mm long) was excised along the longitudinal axis and transferred to a 10 mL isolated organ bath containing Krebs–Henseleit solution of the following millimolar composition: NaCl, 122.4; KCl, 4.56; MgSO 4 7H 2 O, 1.17; CaCl 2 2H 2 O, 2.53; KH 2 PO 4 , 1.15; NaHCO 3 , 24.7 and glucose, 5.5. The solution was maintained at 37°C and gassed with oxygen (95%) and carbon dioxide (5%). Strips were connected to a Basile high sensitivity (Type DY0) force displacement transducer and changes in tension were recorded on a Basile 7050 Unirecord. The detrusor strips were stretched to a passive tension of 1 g and allowed to equilibrate for 60 min. To obtain submaximal, reproducible contrac- tions, after equilibration, tissues were tested for responses to acetylcholine 3.0  10 7 M; 6.0  10 7 M and 1.2  10 6 M. Each concentration was left in contact with the tissue for 1 min and applied twice with a 10 min interval between doses. After washout and a 20 min resting period, isoproter- nol (4.0  10 10 M  EC 50 ) was added to the bath, left in contact with the tissue for at least 5 min, and then washed out. The reproducibility of the response was tested twice with a 30 min interval between doses. Drugs. DL-isoproterenol hydrochloride (isoproterenol) and acetylcholine chloride (ACh) were obtained from Sigma Chemical Co. (St Louis, MO, USA). Drugs were dissolved in deionized water:ethanol (1:1) to make up 2 mg/mL solutions from which dilutions in distilled water were freshly prepared before use. An alcohol extract of Hydrastis canadensis (1:5 weight/volume) was prepared according to Palmery et al. (1996). Alkaloids were isolated from Hydrastis canadensis L. by counter-current PHYTOTHERAPY RESEARCH, VOL. 12, S86–S88 (1998) CCC 0951–418X/98/0S0S86–03 $17.50 # 1998 John Wiley & Sons, Ltd. * Correspondence to: P. Bolle, Institute of Pharmacology and Pharma- cognosy, University of Rome ‘La Sapienza’, P.le A. Moro 5, 00185 Rome, Italy. Accepted 11 June 1997