Thirst and blood pressure regulation in a novel angiotensin II receptor type 1a knockout rat

Figures

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  FIGURE 1. Characteristics of WT and Agtr1a−/− rats. (a) Representative gel illustrating 260 and 249 bp PCR products generated from genomic DNA isolated from ear punch of WT and Agtr1a−/− rats. (b) Mean ± SD and individual data points (male, Ο; female, Χ) of body weight, absolute 24‐h water intake and 24‐h water intake normalized to 100 g body weight. p > 0.05, unpaired t‐test.

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  FIGURE 2. Baseline hemodynamics and regulation of ABP in WT and Agtr1a−/− rats. (a) Mean ± SD and individual data points (male, Ο; female, Χ) of systolic, diastolic, and mean arterial blood pressure (ABP), and heart rate in WT and Agtr1a−/− rats. Unpaired t‐test. (b) Mean ± SD and individual data points (male, Ο; female, Χ) of peak depressor responses after d(CH2)5[Tyr(Me)]AVP (10ug/kg, IV), hexamethonium (30 mg/kg, IV), or captopril (3 mg/kg, IV). Baseline mean ABP before each treatment is provided below each bar graph. Unpaired t‐test.

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  FIGURE 3. Deletion of Agtr1a abolishes thirst and cardiovascular responses induced by intravenous AngII. (a) Mean ± SD and individual data points (male, Ο; female, Χ) of water intake, urinary output, latency to drink, and water intake normalized to body weight during IV infusion of AngII (40 ng/min; 2.5 mL over 60 min) in WT and Agtr1a−/− rats. Two‐way repeated‐measures ANOVA followed by Bonferroni post hoc test and unpaired t‐test. (b) Mean ± SD of mean ABP and heart rate during baseline and throughout AngII infusion. Two‐way repeated‐measures ANOVA followed by Bonferroni post hoc test.

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  FIGURE 4. Deletion of Agtr1a impairs hypotension‐induced thirst. (a) Mean ± SD and individual data points (male, Ο; female, Χ) of water intake, urinary output, latency to drink, and 60‐min cumulative water intake normalized to body weight of WT and Agtr1a−/− rats after injection of diazoxide (DZX; 25 mg/kg, IV). Two‐way repeated‐measures ANOVA followed by Bonferroni post hoc test and unpaired t‐test. (b) Mean ± SD of mean ABP and heart rate during baseline and 60 min after DZX. Two‐way repeated‐measures ANOVA followed by Bonferroni post hoc test.

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  FIGURE 5. Deletion of Agtr1a did not attenuate hypernatremia‐induced thirst. (a) Mean ± SD and individual data points (male, Ο; female, Χ) of water intake, urinary output, latency to drink, and water intake normalized to body weight in response to IV infusion of hypertonic saline (2 M NaCl; 2.5 mL over 30 min) in WT and Agtr1a−/− rats. p > 0.05, two‐way repeated measures ANOVA. p > 0.05, unpaired t‐test. (b) Mean ± SD of mean ABP and heart rate at baseline and during the infusion of hypertonic saline. p > 0.05, two‐way repeated‐measures ANOVA.

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  FIGURE 6. Thirst response to water deprivation is not attenuated in Agtr1a−/− rats. Mean ± SD and individual data points (male, Ο; female, Χ) of water intake after 18–20 h of water deprivation in WT and Agtr1a−/− rats. p > 0.05, two‐way repeated‐measures ANOVA.