Book of Abstracts - New Frontiers 2022

Abstracts of poster presentations

EFFECT OF ALDOSTERONE ANTAGONIST, SPIRONOLACTONE, ON NON DIPPING BLOOD PRESSURE RHYTHM IN HYPERTENSIVE Ren-2 TRANSGENIC RATS

H. Šútovská 1 , Ľ. Molčan 1 , L. Kopkan 2,3 , M. Zeman 1

1 Department of Animal Physiology and Ethology, Faculty of Nature Science, Comenius University, Bratislav, Slovakia; 2 Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; 3 Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic The increased activity of the renin-angiotensin-aldosterone system is an important regulatory mechanism of blood pressure (BP) and leads to hypertension with disturbed 24-hour BP rhythm. Angiotensin II receptor type 1 blockers reduced BP and restored the non-dipping BP profile. The effects of angiotensin II on the 24-hour BP rhythm are mediated directly through vasoconstriction and indirectly through aldosterone synthesis. We aimed to analyse the potency of an aldosterone mineralocorticoid receptor blocker, spironolactone (SPIRO 30 mg/kg/day), on BP and its inverse 24-hour rhythm in male hypertensive Ren-2 transgenic rats (TGR mRen27, control group n = 6, SPIRO group n = 5, 12 weeks old) for 20 days. After 10 days of SPIRO treatment, we increased salt intake (1% in drinking water). BP was continuously measured by telemetry. Spectral power (significance of 24-hour rhythm) and acrophase (the time of rhythm peak) of the 24-hour rhythm of BP were analysed by Chronos-Fit software, and statistical analysis was done by GraphPad Prism software. Administration of SPIRO significantly (p = 0.015) reduced BP (light: 179 ± 4 mmHg, dark: 189 ± 3 mmHg) in TGR after 9 days in comparison with control (light: 192 ± 2 mmH g, dark: 208 ± 3 mmHg) in phase -dependent manner (p < 0.001). High salt intake increased BP (p < 0.05) in the light (control: 228 ± 6 mmHg, SPIRO: 211 ± 9 mmHg) and dark phase (control: 225 ± 7 mmHg, SPIRO: 209 ± 7 mmHg) of the day. SPIRO had no protective effect on the salt-induced increase of BP. SPIRO did not affect the spectral power of the 24- hour BP rhythm (74.5 ± 10.4 vs 67.4 ± 5.8) but tended to decrease the power of BP rhythm (p = 0.061) in combination with salt (80.8 ± 10.3 vs 54.0 ± 15.8). High s alt intake reduced the spectral power of BP in the control (80.8 ± 10.3 vs 6.8 ± 1.8; p < 0.001) and in the SPIRO (54.0 ± 15.8 vs 8.9 ± 1.9; p < 0.001) groups. SPIRO neither affected BP acrophase (4.9 ± 0.3 h vs 5.2 ± 0.5 h) nor in combination with salt (5.0 ± 0.3 h vs 4.4 ± 0.3 h). However, increased salt intake shifted BP acrophase in both, control (5.0 ± 0.3 h vs 21.0 ± 0.5 h; p = 0.001) and SPIRO (4.4 ± 0.3 h vs 25.3 ± 3.8 h; p <0.001) group. In conclusion, SPIRO decreased BP in TGR rats. However, SPIRO did not have a protective effect on BP in combination with high salt intake and did not restore disrupted BP rhythm. Inverse BP rhythm in TGR rats with the up-regulated renin-angiotensin-aldosterone system is not determined by the biological effects of aldosterone, but probably other angiotensin II-dependent post receptor mechanisms.

Keywords: blood pressure, spironolactone, TGR rats, high salt

Funding:Supported by grants: APVV-17-0178 and VEGA 1/0492/19.

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