Pharmacological Effects of Angiotensin 1–7 on Venous Vascular Tone

Figures

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  Figure 1. Experimental workflow and pharmacological protocols used in isolated rat inferior vena cava preparations. (A) After tissue isolation and equilibration, venous rings were precontracted with phenylephrine, followed by methacholine-induced relaxation to verify intact endothelial function. In the first experimental series, Ang II-induced contraction was recorded, after which tissues were incubated with Ang-(1–7) alone or in the presence of pharmacological inhibitors (TEA, indomethacin, or ODQ + L-NAME). Ang II was then re-applied to assess the modulatory effect of Ang-(1–7). (B) In separate experiments, after endothelial assessment, venous rings were precontracted with phenylephrine, endothelin-1, or U46619, followed by cumulative application of Ang-(1–7) (10−9–10−5 M) to evaluate concentration-dependent relaxation.

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  Figure 2. Comparison of representative experimental traces showing the inhibitory effect of Ang-(1–7) on Ang II-induced contractions in inferior vena cava (IVC) rings before and after incubation with Ang-(1–7), and following inhibition with TEA.

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  Figure 3. Effect of Ang-(1–7) pretreatment on Ang II-induced reactivity of isolated IVC rings in vitro and the influence of pharmacological inhibitors. Vascular responses to Ang II were compared between Ang-(1–7)-pretreated and non-treated IVC rings in the absence or presence of L-NAME (eNOS inhibitor), the combination of L-NAME + ODQ (cGMP pathway inhibition), TEA (K+ channel inhibitor), or indomethacin (cyclooxygenase inhibitor). Data are expressed as mean ± SEM of maximal response (Emax, % of precontraction) (n = 8). Direct comparison between Ang-(1–7) + Ang II and Ang-(1–7) + TEA + Ang II was performed to evaluate the contribution of potassium channels. Statistical analysis was performed using one-way ANOVA followed by Tukey’s multiple comparisons test * p < 0.05, and *** p < 0.001 indicate statistical significance versus Ang II alone.

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  Figure 4. Concentration-dependent direct relaxation responses of IVC rings to Ang-(1–7) precontracted with different constrictors. Vessels were precontracted with phenylephrine (PE), U46619 (thromboxane A2 analog), or endothelin-1 (ET-1). Relaxation responses were measured in three experimental groups over a concentration range from 1 nM (10−9 M) to 10 µM (10−5 M). The first point (0) represents the baseline prior to Ang-(1–7) administration. Data are presented as mean ± SEM of maximal relaxation response (n = 8). Relaxation responses are expressed as a percentage (%) of the respective precontraction level (Emax). Statistical significance was evaluated using two-way analysis of variance (ANOVA), followed by a post hoc test of Bonferroni. *** p < 0.001 indicates statistical significance between PE versus ET-1 and U46619. Time-control experiments performed in parallel confirmed overall stability of agonist-induced tone, with only minor, non-significant decline observed in phenylephrine-precontracted rings.