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Modulation of voiding and storage reflexes by activation of alpha1-adrenoceptors
W C de Groat1, M Yoshiyama, A G Ramage
1Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. degroat@server.pharm.pitt.edu
Objective:
This paper reviews recent studies in animals that examined the effect on lower urinary tract function of alpha1-adrenoceptor agonists and antagonists.
Methods:
Bladder reflexes were studied in vivo on anesthetized rats and cats using cystometrographic and electrophysiologic techniques. Neurally-evoked bladder contractions and release of acetylcholine (ACh) were also studied in rat bladder strips in vitro.
Results:
Administration of the alpha1-adrenoceptor agonist, phenylephrine (PE) to isolated strips of rat bladder enhanced neurally-evoked bladder contractions and increased basal tone. The former effects of PE were blocked by a selective alpha1A antagonist and the latter by an alpha1B antagonist. Activation of alpha1A receptors by PE enhanced ACh release evoked by electrical field stimulation in bladder strips. PE also enhanced transmission in cat bladder ganglia. PE or noradrenaline act on alpha- and beta-adrenoceptors on urothelial cells to release nitric oxide. It is concluded that facilitatory alpha1A-adrenoceptors are located prejunctionally in the bladder, whereas alpha1B adrenoceptors are located postjunctionally. In the central nervous system of the rat and cat facilitatory alpha1-adrenergic mechanisms can modulate the sympathetic, parasympathetic and somatic outflow to the urinary tract. In addition inhibitory alpha1 adrenoceptor mechanisms have been detected in the rat spinal cord. Activation of these receptors with PE raises the intravesical pressure threshold for inducing micturition and decreases voiding frequency.
Conclusions:
alpha1-adrenoceptors are located at various sites in the bladder and in the neural pathways controlling lower urinary tract function. At most sites these receptors mediate facilitatory responses that enhance smooth muscle activity or facilitate storage or voiding reflexes. However, alpha1-adrenoceptor inhibitory mechanisms in the rat spinal cord, can also reduce the frequency of voiding reflexes. This effect is possibly mediated by an inhibition in the afferent limb of the micturition reflex pathway.