Rosuvastatin, but not atorvastatin, enhances the antihypertensive effect of cilostazol in an acute model of hypertension

Figures

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  Fig. 1. Effect of acute hypertension induced by intravenous infusion of angiotensin II (AnII) at 120 ng.min−1.kg−1 on systolic blood pressure (SBP, a), diastolic blood pressure (DBP, c), and mean arterial pressure (MAP, e) of adult male Wistar rats and the impact of atorvastatin (Ator) and rosuvastatin (Rosv) on cilostazol (Cilo) effect on elevated SBP (b) of hypertensive rats following slow intravenous injection of Cilo either alone or in combination with Ator or Rosv, at successive doses (0.5, 1, and 2 mg.kg−1), 10 min apart. Also shown the impact of slow intravenous injection of Ator (2 mg.kg−1) and Rosv (2 mg.kg−1) on Cilo (2 mg.kg−1) effect on DBP (d) and MAP (f). Values are presented as mean ± SEM (n = 6/group). *p < 0.05 vs. baseline, #p < 0.05 vs. vehicle treated group, Δp < 0.05 vs. Cilo-treated group, +p < 0.05 vs. Rosv-treated group, and $p < 0.05 vs. Ator-treated group using paired Student t test, one-way ANOVA, and two-way ANOVA followed by Bonferroni post hoc test. Representative images for real time invasive blood pressure (BP) recording (g) are shown. Representative traces from BP recording of baseline and following slow intravenous injection of 2 mg.kg−1 of each drug and…

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  Fig. 2. Effect of acute hypertension induced by intravenous infusion of angiotensin II (AnII) at 120 ng.min−1.kg−1 on pulse pressure (a), dicrotic-notch pressure (c), and systolic blood pressure-dicrotic notch pressure (SDP) difference (e) of adult male Wistar rats and the impact of atorvastatin (Ator) and rosuvastatin (Rosv) on cilostazol (Cilo) effect on pulse pressure (b), dicrotic-notch pressure (d), and SDP difference (f) of hypertensive rats following slow intravenous injection of Cilo either alone or in combination with Ator or Rosv at successive doses (0.5, 1, and 2 mg.kg−1), 10 min apart. Values are presented as mean ± SEM (n = 6/group). *p < 0.05 vs. baseline, #p < 0.05 vs. vehicle-treated group, Δp < 0.05 vs. Cilo-treated group, and +p < 0.05 vs. Rosv-treated group using paired Student t test and two-way ANOVA followed by Bonferroni post hoc test

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  Fig. 3. Effect of acute hypertension induced by intravenous infusion of angiotensin II (AnII) at 120 ng.min−1.kg−1 on heart rate (a), ejection duration (c), and non-ejection duration (e) of adult male Wistar rats and the impact of atorvastatin (Ator) and rosuvastatin (Rosv) on cilostazol (Cilo) effect on heart rate (b), ejection duration (d), and non-ejection duration (f) of hypertensive rats following slow intravenous injection of Cilo either alone or in combination with Ator or Rosv at successive doses (0.5, 1, and 2 mg.kg−1), 10 min apart. Values are presented as mean ± SEM (n = 6/group). *p < 0.05 vs. baseline, #p < 0.05 vs. vehicle-treated group, and $p < 0.05 vs. Ator-treated group using paired Student t test and two-way ANOVA followed by Bonferroni post hoc test

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  Fig. 4. Effect of acute hypertension induced by intravenous infusion of angiotensin II (AnII) at 120 ng.min−1.kg−1 on baroreflex sensitivity demonstrated by spectral domain indexes; square root of the ratio of RRI and SAP in high frequency range (HF-α, a), square root of the ratio of RRI and SAP in low frequency range (LF-α, c), and total sequences of at least three beats in which SAP consecutively increases or decreases accompanied by changes in the RRI of the subsequent beats in the same direction (seq BRS-SAP TOTAL, e) in the sequential domain of adult male Wistar rats. Impact of slow intravenous injection of atorvastatin (Ator, 2 mg.kg−1) and rosuvastatin (Rosv, 2 mg.kg−1) on cilostazol (Cilo, 2 mg.kg−1) effect on HF-α (b), LF-α (d), and seq BRS-SAP TOTAL (f) of hypertensive rats. Values are presented as mean ± SEM (n = 6/group). *p < 0.05 vs. baseline, #p < 0.05 vs. vehicle-treated group, Δp < 0.05 vs. Cilo-treated group, $p < 0.05 vs. Ator-treated group, and.+p < 0.05 vs. Rosv-treated group using paired Student t test and one-way ANOVA followed by Bonferroni post hoc test. SAP (systolic arterial pressure), RRI (beat-to-beat interval)

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  Fig. 5. Effect of acute hypertension induced by intravenous infusion of angiotensin II (AnII) at 120 ng.min−1.kg−1 on heart rate variability demonstrated by standard deviation of beat-to-beat interval (SDRR, a), and root mean square of successive differences (rMSSD, c) and on sympathovagal balance expressed as ratio of power of beat-to-beat interval spectra in low frequency range to that in high frequency range (LFRRI/HFRRI ratio, e) of adult male Wistar rats. Impact of slow intravenous injection of atorvastatin (Ator, 2 mg.kg−1) and rosuvastatin (Rosv, 2 mg.kg−1) on cilostazol (Cilo, 2 mg.kg−1) effect on SDRR (b), rMSSD (d), and LFRRI/HFRRI ratio (f) of hypertensive rats. Values are presented as mean ± SEM (n = 6/group). *p < 0.05 vs. baseline, #p < 0.05 vs. vehicle-treated group, Δp < 0.05 vs. Cilo-treated group, $p < 0.05 vs. Ator-treated group and.+p < 0.05 vs. Rosv-treated group using paired Student t test and one-way ANOVA followed by Bonferroni post hoc test. RRI (beat-to-beat interval)

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  Fig. 6. Impact of slow intravenous injection of atorvastatin (Ator, 2 mg.kg−1) and rosuvastatin (Rosv, 2 mg.kg−1) on cilostazol (Cilo, 2 mg.kg−1) effect on serum nitric oxide (NO, a), norepinephrine (NE, b) sodium (c), and potassium (d) of hypertensive adult male Wistar rats. Acute hypertension was induced by continuous infusion of angiotensin II at 120 ng.min−1.kg−1. Values are presented as mean ± SEM (n = 6/group). #p < 0.05 vs. vehicle-treated group, Δp < 0.05 vs. Cilo-treated group,$p < 0.05 vs. Ator-treated group, and +p < 0.05 vs. Rosv-treated group using one-way ANOVA and Bonferroni post hoc test