Department of Health Sciences, University of Jaén, Jaén, Spain.
Cardiovascular & Metabolic Syndrome Adviser, Rossemaison, Switzerland.
J Hypertens. 2019 Mar;37(3):612-628. doi: 10.1097/HJH.0000000000001884.
Hypertension can lead to mood disorders that may worsen or ameliorate depending on the type of antihypertensive prescribed. Depression is associated with modifications in basal brain asymmetry particularly that of the frontal cortex, which is involved in blood pressure control. Furthermore, different vasoactive drugs may change the brain's asymmetry in a manner that contributes to cognition status. We studied the bilateral activity of several neuropeptidases in frontal cortex as a reflect of the functional status of certain neuropeptides involved in mood.
Using arylamide derivatives as substrates, we fluorometrically analysed the activity of these enzymes in the left and right frontal cortex of control untreated Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs) and compared their activities with WKY or SHR treated with the antihypertensive drugs captopril (CAP) and propranolol (PRO) or with the hypertensive N (G)-nitro-L-arginine methyl ester. SBP was also measured in all WKY and SHR groups.
Untreated WKY, WKY treated with CAP or PRO and SHR treated with CAP exhibited normotensive values of SBP. However, WKY treated with N (G)-nitro-L-arginine methyl ester as well as untreated SHR and SHR treated with PRO and N(G)-nitro-L-arginine methyl ester demonstrated hypertensive values of SBP. Changes in the bilateral distribution of neuropeptidases were depending on the strain, the enzyme analysed and the drug used. Normotensive WKY groups (WKY, CAP, PRO) revealed intrahemispheric correlations mainly in the left hemisphere. In contrast, WKY treated with N(G)-nitro-L-arginine methyl ester and SHR groups demonstrated intrahemispheric correlations mainly in the right hemisphere. Interhemispheric correlations were mostly observed in WKY as well as in SHR groups with antihypertensive treatments (CAP, PRO).
Our results suggest specific brain bilateral patterns of neuropeptidase activities in WKY that change in SHR. This observation may be related to the cognitive disorders that have been described in these animals and that change under antihypertensive or hypertensive drug's treatments.
高血压可能导致情绪障碍,而这些障碍的严重程度可能会因所开的降压药类型而有所不同。抑郁症与基底大脑不对称性的改变有关,特别是与血压控制有关的额叶皮层。此外,不同的血管活性药物可能会以某种方式改变大脑的不对称性,从而影响认知状态。我们研究了额叶皮层中几种神经肽酶的双侧活性,以反映参与情绪的某些神经肽的功能状态。
我们使用芳基酰胺衍生物作为底物,通过荧光法分析了对照组未治疗的 Wistar-Kyoto(WKY)和自发性高血压大鼠(SHR)左、右额叶皮层中这些酶的活性,并将其与用降压药卡托普利(CAP)和普萘洛尔(PRO)治疗的 WKY 或 SHR 或用高血压 N(G)-硝基-L-精氨酸甲酯(N(G)-nitro-L-arginine methyl ester)治疗的 WKY 和 SHR 的活性进行了比较。还测量了所有 WKY 和 SHR 组的 SBP。
未治疗的 WKY、用 CAP 或 PRO 治疗的 WKY 和用 CAP 治疗的 SHR 表现出正常的 SBP 值。然而,用 N(G)-硝基-L-精氨酸甲酯治疗的 WKY、未治疗的 SHR 以及用 PRO 和 N(G)-硝基-L-精氨酸甲酯治疗的 SHR 则表现出高血压的 SBP 值。神经肽酶的双侧分布变化取决于大鼠的品系、所分析的酶和所用的药物。正常血压的 WKY 组(WKY、CAP、PRO)显示出主要在左半球的半球内相关性。相比之下,用 N(G)-硝基-L-精氨酸甲酯治疗的 WKY 和 SHR 组显示出主要在右半球的半球内相关性。在 WKY 和 SHR 组中,用降压药(CAP、PRO)治疗后,主要观察到半球间的相关性。
我们的结果表明,WKY 中存在特定的大脑双侧神经肽酶活性模式,而这些模式在 SHR 中发生了变化。这种观察结果可能与这些动物中描述的认知障碍有关,这些障碍在降压或高血压药物治疗下发生了变化。