Fig. 2: Effects of B38-CAP on plasma angiotensin II levels and blood pressure in mice.

a Plasma B38-CAP levels in mice after intraperitoneal injection of B38-CAP (2 mg kg⁻¹). B38-CAP activity was measured with the B38-CAP substrate Nma-Leu-Pro-Lys(Dnp) (n = 4, 6, 8, 6, 6, and 6 for 0, 1, 2, 4, 8, and 12 h, respectively). b, c Invasive measurements of arterial blood pressure (BP). Experimental protocol (b); mice pretreated with B38-CAP (2 mg kg⁻¹ i.p.) had liquid-filled catheter inserted into carotid artery for BP measurements and Ang II (0.2 mg kg⁻¹ i.p.) was injected and BP measured. Systolic arterial pressure is shown (c). (n = 6 mice per group). d–h Blood pressure measurements with conscious mice. Experimental protocol (d); mice were treated with continuous infusion of vehicle, Ang II (1.5 mg kg⁻¹ per day), B38-CAP (3 mg kg⁻¹ per day), or Ang II (1.5 mg kg⁻¹ per day) plus B38-CAP (3 mg kg⁻¹ per day), and BP was measured by tail-cuff system after 2 weeks. Systolic (e), diastolic (f), and mean (g) BP and heart rate (h) are shown for mice treated vehicle + vehicle (n = 10), vehicle + B38-CAP (n = 11), Ang II + vehicle (n = 11), and Ang II + B38-CAP (n = 11). i–l Measurements of Ang II and Ang 1–7 in the plasma of mice. The plasma was obtained from the mice treated acutely (i, k) and chronically (j, l) with Ang II, in the cohort of b, c, and d–h, respectively. Ang II (i, j) and Ang 1–7 (k, l) levels were measured with ELISA. m BP measurements in conscious mice. The mice pretreated with B38-CAP (2 mg/kg i.p.) at 90 min before acquisition of baseline BP were treated with Ang II (0.2 mg kg⁻¹ i.p.), with or without A779 (0.2 mg kg⁻¹ i.p.). BP was measured every 5 min by tail-cuff system (Supplementary Fig. 9a–d) and the BP at 5 min after the last injection is shown (n = 6 mice per group). All values are means ± SEM. c, e–m, Two-way ANOVA with Sidak’s multiple-comparisons test. Numbers above square brackets show significant P-values.