Centre for Urology Research, Faculty of Health Sciences and Medicine, Bond University, Queensland, 4229, Australia.
Sci Rep. 2020 Mar 5;10(1):4116. doi: 10.1038/s41598-020-60967-7.
Inflammatory mediators may have a role in various lower urinary tract disorders. Histamine is known to induce significant increases in both the tension and frequency of spontaneous phasic contractions in both urothelium with lamina propria (U&LP) and detrusor muscle via the activation of H1 receptor in juvenile animal models. However, it is unclear whether age affects these contractile responses to histamine. This study assessed the histamine receptor subtypes mediating contraction in juvenile and adult porcine bladders and compared the urothelium with lamina propria and detrusor responses to histamine. Isolated tissue bath studies were conducted using strips of porcine U&LP and detrusor obtained from juvenile (6 months) and adult (3 years) animals exposed to histamine receptor agonists and antagonists. Treatment with histamine (100 µM) in U&LP of juvenile animals caused increases in baseline tension by 47.84 ± 6.52 mN/g (p < 0.001, n = 51) and by 50.76 ± 4.10 mN/g (p < 0.001, n = 55) in adult animals. Furthermore, the frequency of spontaneous phasic contractions was significantly enhanced in response to histamine in U&LP of both juvenile and adult tissues (p < 0.001 for both age groups). Treatment with an H2 agonist in U&LP of juvenile animals decreased baseline tension by 13.97 ± 3.45 mN/g (n = 12, p < 0.05), but had no effect in adult animals. Inhibition of H1 receptors resulted in significantly reduced contractile responses of U&LP and detrusor to histamine in both juvenile and adult animals (p < 0.05). Treatment with an H2 receptor antagonist significantly enhanced contractions in juvenile preparations (n = 10, p < 0.05) but had no effect in adult preparations (n = 8). In detrusor, treatment with histamine (100 µM) in juvenile tissues showed a significantly higher increase in baseline tension of 19.10 ± 4.92 mN/g (n = 51) when compared to adult tissues exhibiting increases of 8.21 ± 0.89 mN/g (n = 56, p < 0.05). The increases in the baseline tension were significantly inhibited by the presence of H1 receptor antagonists in both juvenile and adult detrusor preparations. Treatment with either the H2 receptor antagonist or agonist in detrusor had no effect on both juvenile and adult tissues. Therefore, the histamine receptor system may play an essential role in the maintenance of bladder function or in bladder dysfunction observed in some lower urinary tract disorders.
炎症介质可能在各种下尿路疾病中发挥作用。组胺通过激活幼年动物模型中的 H1 受体，已知可显著增加尿路上皮和固有层（U&LP）以及逼尿肌的自发性相位收缩的张力和频率。然而，目前尚不清楚年龄是否会影响这些对组胺的收缩反应。本研究评估了介导幼年和成年猪膀胱收缩的组胺受体亚型，并比较了组胺对 U&LP 和逼尿肌的反应。使用从幼年（6 个月）和成年（3 岁）动物获得的 U&LP 和逼尿肌组织的组织浴分离研究，用组胺受体激动剂和拮抗剂处理。组胺（100µM）处理幼年动物的 U&LP 可使基础张力增加 47.84±6.52mN/g（p<0.001，n=51）和 50.76±4.10mN/g（p<0.001，n=55）。此外，组胺可显著增强 U&LP 中自发性相位收缩的频率在幼年和成年组织中（两个年龄组均 p<0.001）。在幼年动物的 U&LP 中用 H2 激动剂处理可使基础张力降低 13.97±3.45mN/g（n=12，p<0.05），但在成年动物中无作用。H1 受体抑制剂可显著降低幼年和成年动物 U&LP 和逼尿肌对组胺的收缩反应（p<0.05）。用 H2 受体拮抗剂处理可显著增强幼年制剂的收缩（n=10，p<0.05），但对成年制剂无影响（n=8）。在逼尿肌中，组胺（100µM）处理幼年组织显示基础张力增加 19.10±4.92mN/g（n=51），明显高于成年组织的 8.21±0.89mN/g（n=56，p<0.05）。H1 受体拮抗剂的存在可显著抑制基础张力的增加在幼年和成年逼尿肌制剂中。在逼尿肌中用 H2 受体拮抗剂或激动剂处理对幼年和成年组织均无影响。因此，组胺受体系统可能在维持膀胱功能或在一些下尿路疾病中观察到的膀胱功能障碍中发挥重要作用。
