The Phthalic Selenoanhydride Decreases Rat Blood Pressure and Tension of Isolated Mesenteric, Femoral and Renal Arteries

Abstract

Phthalic selenoanhydride (R-Se) solved in physiological buffer releases various reactive selenium species including H₂Se. It is a potential compound for Se supplementation which exerts several biological effects, but its effect on the cardiovascular system is still unknown. Therefore, herein we aimed to study how R-Se affects rat hemodynamic parameters and vasoactive properties in isolated arteries. The right jugular vein of anesthetized Wistar male rats was cannulated for IV administration of R-Se. The arterial pulse waveform (APW) was detected by cannulation of the left carotid artery, enabling the evaluation of 35 parameters. R-Se (1-2 µmol kg^-1), but not phthalic anhydride or phthalic thioanhydride, transiently modulated most of the APW parameters including a decrease in systolic and diastolic blood pressure, heart rate, dP/dt_max relative level, or anacrotic/dicrotic notches, whereas systolic area, dP/dt_min delay, dP/dt_d delay, anacrotic notch relative level or its delay increased. R-Se (~10-100 µmol L^-1) significantly decreased the tension of precontracted mesenteric, femoral, and renal arteries, whereas it showed a moderate vasorelaxation effect on thoracic aorta isolated from normotensive Wistar rats. The results imply that R-Se acts on vascular smooth muscle cells, which might underlie the effects of R-Se on the rat hemodynamic parameters.

Keywords: hemodynamic parameters; phthalic selenoanhydride; rats; vasorelaxation.

Scheme 1

Chemical structures of the three evaluated compounds: phthalic anhydride (R-O) and its sulfur (phthalic thioanhydride, R-S) and selenium (phthalic selenoanhydride, R-Se) isosteres.

Figure 1

Time-dependent changes in 35 rat arterial pulse waveform parameters (APW-Ps) of anaesthetized rats in control (red) and after intravenous administration of 2 µmol kg⁻¹ phthalic anhydride (R-O, green) and its phthalic thioanhydride (R-S, blue) and phthalic selenoanhydride (R-Se, black) isosteres. Abbreviations, definitions, and units of measured APWs from arterial pulse waveform (APW) are as explained previously [51,52] and briefly in Supplementary Material Figure S1.

Figure 1

Time-dependent changes in 35 rat arterial pulse waveform parameters (APW-Ps) of anaesthetized rats in control (red) and after intravenous administration of 2 µmol kg⁻¹ phthalic anhydride (R-O, green) and its phthalic thioanhydride (R-S, blue) and phthalic selenoanhydride (R-Se, black) isosteres. Abbreviations, definitions, and units of measured APWs from arterial pulse waveform (APW) are as explained previously [51,52] and briefly in Supplementary Material Figure S1.

Figure 2

Time-dependent changes of 35 APW-Ps of anaesthetized rats before (red) and after intravenous bolus (15 s) administration of 2 µmol kg⁻¹ R-Se (blue). Vertical dash lines indicate the start of R-Se administration. Abbreviations, definitions, and units of measured APW-Ps from the APW are explained in [51,52] and briefly in Figure S1.

Figure 2

Time-dependent changes of 35 APW-Ps of anaesthetized rats before (red) and after intravenous bolus (15 s) administration of 2 µmol kg⁻¹ R-Se (blue). Vertical dash lines indicate the start of R-Se administration. Abbreviations, definitions, and units of measured APW-Ps from the APW are explained in [51,52] and briefly in Figure S1.

Figure 3

Effect of R-Se on the vascular reactivity of the mesenteric artery ((A) A. mesenterica), femoral artery ((B) A. femoralis), and renal artery ((C) A. renalis). The vasoactive effects of R-Se on the A. mesenterica (A) were pre-contracted with NA (10 µmol L⁻¹), A. femoralis (B) and A. renalis (C) with Ser (1 µmol L⁻¹). The relaxing effect of R-Se was observed for 14−15 min. Comparison of the relaxation effect of R-Se (25 µmol L⁻¹) on mesenteric (Mes.), femoral (Fem.) and renal (Ren.) artery measured at 10.5th min (D). * p < 0.05 vs. DMSO (one-way analysis of variance followed by Tukey-Kramer test for multiple comparisons).

Figure 4

The original records of time-dependent changes in noradrenaline (NA, 0.1 µmol L⁻¹—color curves; 1 µmol L⁻¹—black curves; left arrow)—increased tension of isolated thoracic aorta and the subsequent application of 25 (dotted), 50 (dash), 100 (solid black line), 200 (red, blue, green) and 300 µmol L⁻¹ R-Se (pink). The middle (for colors) and right arrows (for blacks) indicate R-Se application.

Scheme 2

After the stabilization period (B) the vascular segments were contracted with NA (10 µmol L⁻¹, mesenteric artery) or Ser (1 µmol L⁻¹, femoral and renal arteries) and relaxed with gradual addition of acetylcholine (AC, green line, 1 nmol L⁻¹–10 µmol L⁻¹) to test the contractility of the segment. The solution was washed out (W). After the next stabilization period, the segments were again pre-contracted with NA (or Ser) and the effects of R-Se (stock solution, 50 mmol L⁻¹ in DMSO) were added. R-Se was washed out (W) and NA (or Ser) were applied to contract the vascular segment again.