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Rosuvastatin, but not atorvastatin, enhances the antihypertensive effect of cilostazol in an acute model of hypertension.
- Source :
-
Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2024 Apr; Vol. 397 (4), pp. 2321-2334. Date of Electronic Publication: 2023 Oct 11. - Publication Year :
- 2024
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Abstract
- Purpose: Hypertensive emergency, a sudden and severe increase in blood pressure, necessitates immediate intervention to avoid end-organ damage. Cilostazol, a selective phosphodiesterase-III inhibitor, has vasodilator effect. Here, we investigated the effect of two commonly used statins, atorvastatin or rosuvastatin, on cilostazol antihypertensive activity in acute model of hypertension.<br />Methods: Hypertensive emergency was induced via angiotensin II intravenous infusion (120 ng.kg <superscript>-1</superscript> .min <superscript>-1</superscript> ). Rats were subjected to real-time arterial hemodynamics and electrocardiogram recording while investigated drugs were injected slowly at cumulative doses 0.5, 1, and 2 mg.kg <superscript>-1</superscript> , individually or in combination, followed by baroreflex sensitivity (BRS) analysis and serum electrolytes (Na <superscript>+</superscript> and K <superscript>+</superscript> ) and vasomodulators (norepinephrine (NE), and nitric oxide (NO)) assessment.<br />Results: Cilostazol reduced systolic blood pressure (SBP), while co-injection with rosuvastatin augmented cilostazol SBP-reduction up to 30 mmHg. Compared to atorvastatin, rosuvastatin boosted the cilostazol-associated reduction in peripheral resistance, as evidenced by further decrease in diastolic, pulse, and dicrotic-notch pressures. Rosuvastatin co-injection prevented cilostazol-induced changes of ejection and non-ejection durations. Additionally, rosuvastatin coadministration produced better restoration of BRS, with an observed augmented increase in BRS indexes from spectral analysis. Greater reduction in sympathetic/parasympathetic ratio and serum NE upon rosuvastatin coadministration indicates further shift in sympathovagal balance towards parasympathetic dominance. Additionally, rosuvastatin coinjection caused a greater decrease in serum sodium, while more increase in NO indicating augmented reduction of extracellular volume and endothelial dysfunction.<br />Conclusion: Rosuvastatin boosted cilostazol's antihypertensive actions through effects on peripheral resistance, BRS, sympathovagal balance, endothelial dysfunction, and electrolytes balance, while atorvastatin did not demonstrate a comparable impact.<br /> (© 2023. The Author(s).)
Details
- Language :
- English
- ISSN :
- 1432-1912
- Volume :
- 397
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Naunyn-Schmiedeberg's archives of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 37819392
- Full Text :
- https://doi.org/10.1007/s00210-023-02758-1