Altered regulation of bladder nerve growth factor and neurally mediated hyperactive voiding.
Elevated bladder smooth muscle cell (BSMC) nerve growth factor (NGF) secretion and related neuroplasticity are associated with hyperactive voiding in spontaneously hypertensive rats (SHRs: hypertensive, behaviorally hyperactive), compared with control Wistar-Kyotos (WKYs). We used two inbred strains (WKHT: hypertensive; WKHA: hyperactive) to further investigate this phenomenon. WKHA BSMCs secreted higher basal levels of NGF than WKHT BSMCs. Antagonists did inhibit NGF output in WKHA but not WKHT cultures. Thus augmented basal secretion of NGF cosegregates with a hyperactive phenotype, whereas a lack of regulatory inhibition of NGF output cosegregates with a hypertensive phenotype. Bladder norepinephrine content paralleled NGF content, with WKHTs > SHRs > WKHAs > WKYs, providing evidence that a lack of inhibition is the greatest contributor to elevated bladder NGF and noradrenergic innervation. Protein kinase C (PKC) agonists affected NGF production differentially depending on strain, suggesting that altered PKC signaling may contribute to strain differences in NGF secretion. Finally, 6-h voiding frequency differed between the strains, with SHRs > WKHTs = WKHAs > WKYs. Thus aspects of both the hypertensive and hyperactive phenotypes may be associated with elevated SHR bladder NGF and hyperactive voiding.
Clemow
D B
DB
Department of Neuroscience, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.
Steers
W D
WD
McCarty
R
R
Tuttle
J B
JB
D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D009473:Neuronal Plasticity; D009478:Neuropeptide Y / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D014554:Urination / Q000502:physiology*; D014555:Urination Disorders / Q000503:physiopathology*
D009414:Nerve Growth Factors; D009478:Neuropeptide Y; D010982:Platelet-Derived Growth Factor; D005576:Colforsin; D010656:Phenylephrine; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate