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. Author manuscript; available in PMC: 2022 Feb 1.
Published in final edited form as: Hypertension. 2020 Nov 30;77(2):420–431. doi: 10.1161/HYPERTENSIONAHA.120.15793

Figure 6: Effect of acute ICV infusion of TRV027 on systolic blood pressure and heart rate.

Figure 6:

A. Telemetry-instrumented mice were subjected to a surgical implantation of a DOCA pellet and a stainless steel ICV cannula, which facilitates the repeated administration of drugs into the lateral ventricle. Subsequently, baseline blood pressure (BP) and HR were recorded, and mice were tested for the acute responses to a central injection of either vehicle (aCSF), TRV027, or losartan (Los). The systolic, diastolic and mean BP and HR were recorded for the duration of one-hour post-injection. Two days were given for the complete clearance of the preceding drug before a new drug was tested. B-C. Panel 1: SBP (B) and HR (C) were recorded for the duration of one-hour post-injection of either vehicle (aCSF), TRV027, or Los. Data were analyzed by mixed effects model and Dunnett’s multiple comparisons procedure. Panel 2: ΔSBP and ΔHR were calculated by subtracting the baseline SBP and HR at t=0 min from the SBP and HR at any given time t(i). A Mixed effects model with repeated measure and post-hoc Dunnett test was performed to compare the SBP or ΔSBP at each t(i) compared with the control SBP or ΔSBP at t=0 and to compare the HR or ΔHR for each t(i) compared with the control HR or ΔHR at t=0 for each experimental group. Panel 3: Peak responses for TRV027 and Los injections were defined as the drop in ΔSBP or ΔHR that were significantly different from vehicle injection. Peak ΔSBP occurred at 25 min for los and 40 for TRV027 injections, respectively. Peak ΔHR occurred at 30 min for los and 40 min for TRV027 injections. Mixed effects model with post-hoc Tukey-Krammer test was performed to compare the ΔSBP and the ΔHR between TRV027, Los and aCSF injection at each timepoint. Panel 4: The area under the curve (AUC) for ΔSBP or ΔHR are shown. One-way ANOVA with post-hoc Tukey’s test was performed to compare the AUC. Adjusted p<0.05 was considered significant. #p<0.05 compared with Los injection at t=0, *p<0.05 compared with TRV027 at t=0. $p<0.05 compared with aCSF at 30 min; ϕp<0.05 compared with aCSF at 40 min. πp<0.05 compared with aCSF. N values are: aCSF (n=6), TRV027 (n=5), and Los (n=5).