Effects of nepicastat upon dopamine-beta-hydroxylase activity and dopamine and norepinephrine levels in the rat left ventricle, kidney, and adrenal gland

• Type: Article in International Scientific Journal
• Date: 2020

Authors

Catelas, DN (Author) Other; Maria Paula Serrão (Author) FMUP; soares-da-silva, p (Author) FMUP

Journal

Title: Clinical and Experimental Hypertension

Vol. 42

Pages: 118-125

ISSN: 1064-1963

Publisher: Taylor & Francis

Indexing

ISI Web of Knowledge - 0 Citations

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Other information

Authenticus ID: P-00Q-B5K

DOI: 10.1080/10641963.2019.1583245

Abstract (EN): Background and Objective: Evaluate the activity of dopamine-beta-hydroxylase (D beta H) as well as the effect of the D beta H inhibitor nepicastat upon enzyme activity and levels of dopamine (DA) and norepinephrine (NE) in the rat left ventricle, kidney, and adrenal glands. Methods: D beta H assay consisted of the enzymatic hydroxylation of tyramine into octopamine, and DA and NE tissues levels were quantified by HPLC-ED. Results: Nepicastat (30 mg/kg, p.o.) reduced D beta H activity by 93% and 80% in the adrenals at 4 h and 8 h postdrug administration, accompanied by significant reductions in NE and epinephrine tissue levels and an increase in DA levels and of DA/NE tissue ratios, with similar findings for NE, DA and of DA/NE tissue ratios in left ventricle and kidney. D beta H activity in the left ventricle and kidney showed a high degree of variability, which does not allow corroboration of the effects of nepicastat upon catecholamine tissue levels. Conclusion: The assay of D beta H activity in heart and kidney lacks the necessary robustness, but D beta H activity in the adrenals appears to be an appropriate marker. However, the effect size upon DA/NE tissue ratios (an indirect measure of D beta H activity) as induced by nepicastat was very similar in sympathetically innervated tissues, left ventricle and kidney, and the adrenal medulla.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8