Impaired Excitatory Neurotransmission in the Urinary Bladder from the Obese Zucker Rat: Role of Cannabinoid Receptors.
Metabolic syndrome (MS) is a known risk factor for lower urinary tract symptoms. This study investigates whether functional and expression changes of cannabinoid CB1 and CB2 receptors are involved in the bladder dysfunction in an obese rat model with insulin resistance. Bladder samples from obese Zucker rat (OZR) and their respective controls lean Zucker rat (LZR) were processed for immunohistochemistry and western blot for studying the cannabinoid receptors expression. Detrusor smooth muscle (DSM) strips from LZR and OZR were also mounted in myographs for isometric force recordings. Neuronal and smooth muscle CB1 and CB2 receptor expression and the nerve fiber density was diminished in the OZR bladder. Electrical field stimulation (EFS) and acetylcholine (ACh) induced frequency- and concentration-dependent contractions of LZR and OZR DSM. ACh contractile responses were similar in LZR and OZR. EFS-elicited contractions, however, were reduced in OZR bladder. Cannabinoid receptor agonists and antagonists failed to modify the DSM basal tension in LZR and OZR In LZR bladder, EFS responses were inhibited by ACEA and SER-601, CB1 and CB2 receptor agonists, respectively, these effects being reversed by ACEA plus the CB1 antagonist, AM-251 or SER-601 plus the CB2 antagonist, AM-630. In OZR bladder, the inhibitory action of ACEA on nerve-evoked contractions was diminished, whereas that SER-601 did not change EFS responses. These results suggest that a diminished function and expression of neuronal cannabinoid CB1 and CB2 receptors, as well as a lower nerve fiber density is involved in the impaired excitatory neurotransmission of the urinary bladder from the OZR.
Departamento de Urología, Hospital General Universitario Gregorio Marañón, 28007-Madrid.
Igor
I
Blaha
Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid.
Paz
P
Recio
Departamento de Anatomía y Anatomía Patológica Comparadas, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040-Madrid.
María Pilar
MP
Martínez
Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid.
María Elvira
ME
López-Oliva
Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid.
Ana S F
AS
Ribeiro
Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid.
Ángel
Á
Agis-Torres
Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid.
Ana Cristina
AC
Martínez
Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid.
Sara
S
Benedito
Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid.
Albino
A
García-Sacristán
Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid.
Vítor S
VS
Fernandes
Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid.
Medardo
M
Hernández
D000818:Animals; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000294:innervation / Q000473:pathology / Q000503:physiopathology; D009412:Nerve Fibers / Q000473:pathology; D009765:Obesity / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D011924:Rats, Zucker; D043884:Receptor, Cannabinoid, CB1 / Q000032:analysis* / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000032:analysis* / Q000378:metabolism; D009435:Synaptic Transmission; D001743:Urinary Bladder / Q000294:innervation* / Q000473:pathology / Q000503:physiopathology*
D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2