A role for muscarinic receptors or rho-kinase in hypertension associated rat bladder dysfunction?
OBJECTIVE
Essential arterial hypertension is a frequent condition. Spontaneously hypertensive rats (SHRs) show bladder dysfunction similar to that seen in patients with overactive bladder. Since muscarinic receptors and rho-kinase have a key role in the regulation of bladder contractility, we determined whether alterations of either one might contribute to hypertension associated bladder dysfunction.


METHODS
The bladders of SHRs and normotensive Wistar Kyoto rats (WKYs) were compared in in vitro radioligand binding and contractility studies.


RESULTS
The mean total number of muscarinic receptors +/- SEM (181 +/- 14 vs 191 +/- 22 fmol/mg protein) and the relative roles of their subtypes were similar in SHRs and WKYs. Contractile responses to the muscarinic agonist carbachol (maximum effect 2.04 +/- 0.24 vs 2.05 +/- 0.14 mN/mm strip length and -log EC50 5.61 +/- 0.07 vs 5.64 +/- 0.04) and to KCl in a receptor independent manner were similar in the 2 strains. The M3 selective antagonist darifenacin inhibited carbachol responses much more potently than the M2 selective antagonist methoctramine but the potency of the 2 drugs was similar in each strain. The rho-kinase inhibitor Y27,632 attenuated carbachol induced contraction in a quantitatively similar manner in SHRs and WKYs.


CONCLUSIONS
An altered function of muscarinic receptor subtypes or rho-kinase does not appear to contribute to bladder dysfunction in SHRs.
Schneider
Tim
T
Department of Urology and Medicine, University of Essen, Essen, Germany.
Hein
Peter
P
Bai
Jie
J
Michel
Martin C
MC
D000818:Animals; D004195:Disease Models, Animal; D006973:Hypertension / Q000150:complications* / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011976:Receptors, Muscarinic / Q000502:physiology*; D014549:Urinary Incontinence / Q000503:physiopathology*; D014563:Urodynamics / Q000502:physiology*; D054460:rho-Associated Kinases
D047908:Intracellular Signaling Peptides and Proteins; D011976:Receptors, Muscarinic; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases