Blood pressure decrease in spontaneously hypertensive rats folowing renal denervation or dopamine beta-hydroxylase inhibition with etamicastat

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Pires, NM (Author) Other; Igreja, B (Author) Other; Moura, E (Author) Other; Wright, LC (Author) Other; Maria Paula Serrão (Author) FMUP; Soares da Silva, P (Author) Other

Journal

Title: Hypertension Research

Vol. 38

Pages: 605-612

ISSN: 0916-9636

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 13 Citations

Scopus - 4 Citations

Other information

Authenticus ID: P-00G-NE0

DOI: 10.1038/hr.2015.50

Abstract (EN): Overactivity of the sympathetic nervous system has an important role in the development and progression of arterial hypertension. Catheter-based renal nerve ablation for the treatment of drug-resistant hypertension has recently been developed. An alternative strategy for the modulation of sympathetic nerve function is to reduce the biosynthesis of noradrenaline (NA) by inhibiting dopamine a-hydroxylase (D beta H), the enzyme that catalyzes the conversion of dopamine (DA) to NA in the sympathetic nerves. Renal denervation (RDN) surgery was performed in spontaneously hypertensive rats (SHR) to evaluate the effect of RDN on the DA and NA levels and on blood pressure over a 28-day period. The selective peripheral D beta H inhibitor etamicastat (30 mg kg(-1) day(-1)) was administered to another cohort of SHR. RDN and etamicastat treatment had no effect on the renal function, as assessed by measuring the water balance response, renal function and urinary electrolyte levels. RDN significantly decreased the systolic blood pressure (SBP) and the diastolic blood pressure (DBP). A gradual return of the SBP and the DBP to the high baseline levels was observed over time. Conversely, treatment with etamicastat resulted in a significant decrease in the SBP and the DBP at all time points. On the last day of the assessment, NA levels in renal tissue were significantly decreased in both RDN and etamicastat-treated groups. In contrast, the NA levels in the left ventricle were decreased only in the etamicastat-treated group. Thus, RDN produces transitory decreases in blood pressure, whereas prolonged downregulation of sympathetic drive with the D beta H inhibitor etamicastat results in a sustained decrease in the SBP and the DBP.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8