The influence of doxazosin, an α1-adrenergic receptor antagonist on the urinary bladder contractility in pigs

Abstract

In the present study influence of doxazosin on the porcine urinary bladder contractility has been examined. Immature pigs were treated for 30 days with: a) doxazosin (n = 5) per os at a dose of 0.1 mg/kg b.w. or b) placebo (n = 5; control group). Thereafter, animals were sacrificed and urinary bladder strips from the trigone were suspended in organ baths. The tension of the smooth musce was measured before and after exposition to acetylocholine (ACh; 10 -5 -10 -3 M), norepinephrine (NE; 10 -9 -10 -7 M) and 5-hydroxytryptamine (5-HT; 10 -7 -10 -5 M). Both the ACh and 5-HT at the highest doses significantly increased the contractility in each group, but this response was weaker in doxazosin-treated animals. NE caused relaxation in both groups, but the effect was weaker in doxazosine-treated group. The results of our study have shown that long-term administration of doxazosin caused a desensitization of the detrusor smooth muscle for in vitro applied mediators of the autonomic nervous systems.

Effects of Dietary Vitamin E Supplementation in Bladder Function and Spasticity during Spinal Cord Injury

“…In this context, we evaluate whether bladder dysfunction was a good target for this treatment. Current interventions used to reduce bladder dysfunction after SCI include cholinergic muscarinic receptor antagonists [ 79 , 80 , 81 , 82 , 83 , 84 , 85 ], chemical blockade of C-fiber afferent neurotransmission with capsaicin or resiniferatoxin [ 86 , 87 , 88 , 89 , 90 , 91 , 92 ] and alpha1- acetylcholine receptor (AR) receptor antagonists [ 93 , 94 , 95 , 96 , 97 , 98 , 99 ]. Additional interventions include suppression of motorneuron or interneuron excitation in the spinal cord by glycine, GABA agonists, and baclofan is being used to treat dysfunctional contraction of the external urethral sphincter [ 100 , 101 , 102 , 103 , 104 , 105 , 106 ].…”

Doxazosin attenuates renal matrix remodeling mediated by anti-α1-adrenergic receptor antibody in a rat model of diabetes mellitus

“…Autoantibodies were detected using an enzyme-linked immunoabsorbent assay (ELISA). Anti-α 1 -R autoantibodies were detected as previously described ( 28 – 30 , 32 ). Peptide segments of the second extracellular loop of the α 1 -R amino acid sequence were synthesized that comprised of residual segments of amino acids at sites 192–218 of α 1 -R (amino acid residue sequence, G-W-K-E-P-V-P-P-D-E-R-F-C-G-I-T-E-E-A-G-Q-A-V-F-S-S-V).…”

“…In the present study, rat models of DM were used to determine the effects of α 1 -R Ab on renal matrix remodeling in rats, as well as the potential effects of doxazosin, which is an α 1 -adrenergic receptor blocker ( 30 ), in the attenuation of renal matrix remodeling and aberrant renal functions. The potential role of TGF-β 1 and the effects of doxazosin on the pathogenesis of DN were also evaluated.…”

The influence of doxazosin on the contractility of the urinary bladder in female pigs with experimentally induced cystitis

“…Thereafter, the strips were incubated with either 5-HT (10 -6 -10 -4 M; Sigma-Aldrich, Germany), ACh (10 -5 -10 -3 M; Sigma-Aldrich), or NE (10 -9 -10 -7 M; Polfa, Poland). The doses of the substances tested were determined based on results of the previous study (Markiewicz et al 2014). The contractile activity was measured for 10 min before and after administration of each concentration.…”

“…Our previous study has shown that long-term (30 days) oral administration to pigs of doxazosin caused a desensitization of the detrusor smooth muscle to in vitro applied 5-hydroxytryptamine (5-HT), acetylocholine (ACh) and norepinephrine (NE) (Markiewicz et al 2014). Although the domestic pig has become a critically important experimental animal in biomedical research (Swindle et al 2012), there is still lack of data concerning the influence of α 1 -adrenergic receptors on the inflammation of the urinary bladder.…”