The spontaneously hypertensive rat: insight into the pathogenesis of irritative symptoms in benign prostatic hyperplasia and young anxious males

Abstract

SUMMARY Recent epidemiological studies have shown that hypertensive men are more likely to undergo surgical intervention for irritative voiding symptoms from BPH than age‐matched controls. Indeed, noradrenergic nerves which regulate vascular tone also participate in the functional component of bladder outlet obstruction due to BPH. Newer, less invasive therapies for BPH such as thermal therapy can relieve symptoms yet do not eliminate obstruction based on urodynamic studies. Coincidentally, drugs such as α‐adrenoceptor antagonists, which have been thought to relieve obstruction due to a peripheral effect, can be given intrathecally in animals to relieve urinary frequency due to obstruction. Taken together these observations implicate both peripheral and central sympathetic pathways in the motor control of the urinary bladder especially with disease states. We have used the hypertensive and behaviourally hyperactive spontaneously hypertensive rat (SHR), to investigate the roles sympathetic pathways or micturition. Elevated nerve growth factor (NGF) derived from vascular and bladder smooth muscle cells of the SHR appears to direct morphological, biochemical, and functional changes. The increase in NGF can apparently be explained by stabilization of its mRNA leading to increased synthesis of NGF. Bladders from SHRs develop a profuse noradrenergic hyperinnervation compared with the control WKY strain. Since afferents supplying the SHR bladder are hypertrophied, changes in afferent pathways are also likely. These differences in innervation and NGF in the SHR may explain changes in function. SHRs void 3 times as frequently as their genetic controls. Urinary frequency can be reduced by α‐adrenoceptor antagonists. Cystometrograms performed in SHRs reveal lower bladder capacities and micturition volumes and the presence of unstable contractions compared with the WKY rat. Intrathecal, rather than intra‐arterial administration of the α‐adrenoceptor antagonist doxazosin reduces unstable contractions in the SHR. In vitro muscle bath studies have shown enhanced responses of SHR bladder smooth muscle to α‐adrenoceptor agonists. It is likely that upregulation of NGF production causes sensory and possibly noradrenergic pathways to elicit hyperactive voiding. Increase in NGF in the adult bladder due to pathological conditions yields similar, yet distinct, consequences for voiding behaviour and innervation. Likewise, increased NGF in adult bladders following obstruction or inflammation triggers neuronal hypertrophy, enhanced reflex activity and urinary frequency. In contrast to the SHR, hyper‐innervation is not observed. Moreover, peripheral or spinal α‐adrenoceptor blockade eliminates urinary frequency following obstruction. These observations support the role for sympathetic pathways in the motor function of the bladder, especially in congenital or adult disease states. A similar process may underlie the neuroplasticity involved in alterations after obstruction or inflammation of the lower urinary tract in humans. The SHR strain ...

<b>Naftopidil improves locomotor activity and urinary frequency in rats with pelvic venous </b><b>congestion </b>

“…When examining hypertension, the relevance of lower urinary tract symptoms and their association with hypertension need to be taken into consideration. Spontaneously hypertensive rats have been shown to have a significantly lower bladder capacity and voiding volume (24), and these rats also exhibit the abdomen, all animals were given a subcutaneous injection of an antibiotic (30 mg of ampicillin). The 16 rats in this group were then randomly divided into the PC and the PC/naftopidil group (n = 8 in each group).…”

α1-Adrenoceptor selectivity and the treatment of benign prostatic hyperplasia and lower urinary tract symptoms

“…91 Catecholaminē uorescent staining of bladders from SHRs demonstrates that they have increased noradrenergic innervation compared with their genetic controls (WKY). 88 This is supported by the increased noradrenaline tissue content observed in bladders and prostates from SHRs compared with WKY controls. 92 Elevated levels of NGF are also found in bladders of SHRs.…”

“…86 Interestingly, prostates from SHRs demonstrate prostatic hyperplasia, 87 and SHRs exhibit urinary frequency and unstable bladder contractions. 88 In secondgeneration (F1) rats resulting from cross-breeding between SHR and their genetic counterparts Wistar ± Kyoto (WKY), blood pressure was found to correlate with urinary frequency. 89 SHRs exhibit increased urinary frequency compared with control rats, independent of age and bladder size, 90 together with non-micturition contractions and reduced sensory volume/pressure thresholds.…”

Benign prostatic hyperplasia: dietary and metabolic risk factors

“…Recent epidemiological studies have shown that hypertensive men are more likely to undergo surgical intervention for irritative voiding symptoms from BPH than agematched controls. These studies have hypothesized that noradrenergic nerves, which regulate vascular tone also participate in the functional component of bladder outlet obstruction due to BPH [39]. In a retrospective study involving 423 BPH cases, hypertension was detected in 128 cases (30.3%) and significant positive correlations were found between prostate volume and years of hypertension.…”