Spinal and peripheral mechanisms contributing to hyperactive voiding in spontaneously hypertensive rats.
The influence of noradrenergic mechanisms involved in micturition in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats was investigated using continuous cystometry in in vivo and in vitro studies on isolated bladder and urethral tissues. Compared with WKY rats, SHR had a significantly lower bladder capacity (SHR: 0.7 +/- 0. 05 ml; WKY rats: 1.3 +/- 0.06 ml; P < 0.001), micturition volume (SHR: 0.4 +/- 0.04 ml, WKY rats: 1.2 +/- 0.05 ml; P < 0.001), and an increased amplitude of nonvoiding (unstable) bladder contractions. The effects of intrathecal and intra-arterial doxazosin on cystometric parameters were more pronounced in SHR than in WKY rats. There was a marked reduction in nonvoiding contractions after intrathecal (but not intra-arterial) doxazosin in SHR. Norepinephrine (0.1 microM-1 mM) failed to evoke contractions in bladder strips from WKY rats, in contrast to a weak contractile response in SHR. The response to electrical field stimulation was significantly less in bladder strips from SHR than from WKY rats. In WKY rats, norepinephrine produced concentration-dependent inhibition (87 +/- 5%, n = 6) of nerve-evoked bladder contractions. Almost no inhibition (11 +/- 8%, n = 6) was found in SHR. Alterations in bladder function of SHR appear to be associated with changes in the noradrenergic control of the micturition reflex, in addition to an increased smooth muscle and decreased neuronal responsiveness to norepinephrine. The marked reduction in nonvoiding contractions after intrathecal doxazosin suggests that the bladder hyperactivity in SHR has at least part of its origin in supraspinal and/or spinal structures.
Department of Clinical Pharmacology, Lund University Hospital, S-221 85 Lund, Sweden.
K
K
Persson
R K
RK
Pandita
J M
JM
Spitsbergen
W D
WD
Steers
J B
JB
Tuttle
K E
KE
Andersson
D000818:Animals; D001835:Body Weight; D004231:Diuresis; D005260:Female; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D066298:In Vitro Techniques; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000502:physiology / Q000503:physiopathology*; D009929:Organ Size; D010525:Peripheral Nerves / Q000502:physiology / Q000503:physiopathology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013116:Spinal Cord / Q000502:physiology / Q000503:physiopathology*; D014521:Urethra / Q000502:physiology / Q000503:physiopathology; D001743:Urinary Bladder / Q000502:physiology / Q000503:physiopathology*; D014554:Urination / Q000502:physiology*; D014555:Urination Disorders / Q000209:etiology / Q000503:physiopathology