A Human Atrial Natriuretic Peptide Gene Mutation Reveals a Novel Peptide With Enhanced Blood Pressure-Lowering, Renal-Enhancing, and Aldosterone-Suppressing Actions
Paul M. McKie, MD*,*,
Alessandro Cataliotti, MD, PhD*,
Brenda K. Huntley, BS*,
Fernando L. Martin, MD*,
Timothy M. Olson, MD and
John C. Burnett, Jr, MD*
* Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minnesota
Cardiovascular Genetics Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minnesota
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Figure 2 In Vitro cGMP Generation in Response to ANP and mANP
In vitro 3',5'-cyclic guanosine monophosphate (cGMP) generation in cultured human cardiac fibroblasts in response to ANP (blue bar) and mANP (red bars) compared with controls (no treatment) (open bar). Values are mean ± SEM. *p < 0.05 versus control by unpaired t tests. Abbreviations as in Figure 1.
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Figure 3 Renal Excretory Response to High-Dose ANP and mANP
(A) Urine flow (UV), (B) urine sodium excretion (UNaV), and (C) distal tubular fractional sodium reabsorption (DFNaR) after infusion of high-dose (33 pmol/kg/min) ANP (blue lines) and mANP (red lines) in normal dogs. Values are mean ± SEM. *p < 0.05 versus baseline by 1-way analysis of variance (ANOVA). p < 0.05 for mANP versus ANP at a specific time point as measured by 2-way ANOVA and Bonferroni post-tests. The p value shown represents the main group effect between ANP and mANP as measured by 2-way ANOVA. BL = baseline; infusion = infusion of high-dose (33 pmol/kg/min) mANP or ANP; Rec 1 = 30 to 60 min post-infusion; Rec 2 = 60 to 90 min post-infusion; Rec 3 = 90 to 120 min post-infusion; WO = washout (0 to 30 min post-infusion); other abbreviations as in Figure 1.
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Figure 4 RAA Response to High-Dose ANP and mANP
Measurement of the renin-angiotensin-aldosterone (RAA) system after infusion of high-dose (33 pmol/kg/min) ANP (blue lines) and mANP (red lines) in normal dogs: (A) plasma renin activity, (B) angiotensin II, and (C) aldosterone. Values are mean ± SEM. *p < 0.05 versus baseline by 1-way ANOVA. The p value shown represents the main group effect between ANP and mANP as measured by 2-way ANOVA. Abbreviations as in Figures 1 and 3.
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Figure 5 Urinary ANP Immunoreactivity Excretory Response to ANP and mANP
Urinary atrial natriuretic peptide immunoreactivity excretion (UANPV) after infusion of (A) high-dose (33 pmol/kg/min) and (B) low-dose (2 pmol/kg/min) ANP (blue lines) and mANP (red lines). Values are mean ± SEM. *p < 0.05 versus baseline by 1-way ANOVA. p < 0.05 for mANP versus ANP at a specific time point as measured by 2-way ANOVA and Bonferroni post-tests. The p value shown represents the main group effect between ANP and mANP as measured by 2-way ANOVA. Infusion = infusion of low-dose or high-dose mANP or ANP; other abbreviations as in Figures 1 and 3.
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Figure 6 Renal Excretory Response to Low-Dose ANP and mANP
(A) Urine flow (UV), (B) urine sodium excretion (UNaV), and (C) distal tubular fractional sodium reabsorption (DFNaR) after infusion of low-dose (2 pmol/kg/min) ANP (blue lines) and mANP (red lines) in normal dogs. Values are mean ± SEM. *p < 0.05 versus baseline by 1-way ANOVA. p < 0.05 for mANP versus ANP at a specific time point as measured by 2-way ANOVA and Bonferroni post-tests. The p value shown represents the main group effect between ANP and mANP as measured by 2-way ANOVA. Infusion = infusion of low-dose (2 pmol/kg/min) mANP or ANP; other abbreviations as in Figures 1 and 3.
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