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Effects of nifedipine on renal responses to human atrial natriuretic peptide in healthy subjects and normoglycemic patients with type 1 diabetes mellitus

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Summary

We examined renal responses to a pharmacological dosage of human atrial natriuretic peptide (hANP) and the potential interference of nifedipine administration with the effects of hANP on kidney function in healthy subjects and normoglycemic patients with type 1 diabetes mellitus. Ten healthy volunteers (age, 28±1 years) and ten patients (age, 33±2 years; diabetes duration; 14±3 years; HbAI 7.2%±0.2%) were studied. According to a double-blind, randomized, placebo-controlled trial design, three experiments were performed in each subject using the doubledummy technique: placebo only, hANP only, and nifedipine+hANP. As i.v. bolus injection 100 µg hANP was given; nifedipine was applied buccally, at a dose of 10 mg 90 min before and at a dose of 5 mg together with hANP injection. At base-line and in the placebo only experiment, patients did not differ from controls. In the hANP only experiment, in both groups hANP resulted in increased urinary volume and both sodium and chloride excretion (P<0.05 vs placebo only experiment). In patients, hANP-induced increase in electrolyte excretion was greater than in controls (P<0.05). In the nifedipine + hANP experiment, hANP-induced changes in renal indexes were enhanced in controls (P<0.05 vs hANP only experiment) but not in patients. Thus, diuretic response to nifedipine + hANP in patients was decreased in comparison with controls (P<0.05). In patients, however, nifedipine administration decreased the hANP-induced increase in urinary albumin excretion (P<0.05 vs hANP only experiment). Creatinine clearance was uninfluenced throughout the experiments.

There were similar decreases in blood pressure in patients and controls after nifedipine administration (P<0.05 vs placebo only experiment). The increase in heart rate after nifedipine was more pronounced in patients than in controls (P<0.05). Conversely, plasma renin activity was stimulated by nifedipine only in controls (P<0.05 vs placebo only experiment). In this study hANP had no effect on heart rate, blood pressure, or plasma renin activity. There was a short-term increase in hANP levels in plasma after nifedipine administration in controls (P<0.05 vs placebo only experiment) but not in patients. In contrast to a previous study, where renal responses to the same pharmacological dosage of hANP were decreased in patients with type 1 diabetes mellitus with HbAI exceeding the normal range, there is no impairment of renal responsiveness to an i.v. bolus of hANP in patients with HbAI within the normal range. Nifedipine and hANP have synergistic effects on kidney function in healthy subjects. It remains to be studied, however, by which mechanism(s) this synergism could be obscured in diabetes patients. Moreover, the increase in hANP levels after nifedipine administration exclusively in controls merits further investigation.

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Abbreviations

hANP:

Human atrial natriuretic peptide

HbAI:

Glycosylated hemoglobin AI

HbAI c:

Glycosylated haemoglobin AI c

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  1. Zentrum der Inneren Medizin, Johann Wolfgang Goethe-Universität Frankfurt am Main, Germany

    E. Jungmann, K. Seel, E. Hofmann, E. -H. Scheuermann & K. Schöffling

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  1. E. Jungmann
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  2. K. Seel
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  3. E. Hofmann
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  4. E. -H. Scheuermann
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  5. K. Schöffling
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Jungmann, E., Seel, K., Hofmann, E. et al. Effects of nifedipine on renal responses to human atrial natriuretic peptide in healthy subjects and normoglycemic patients with type 1 diabetes mellitus. Klin Wochenschr 67, 1174–1181 (1989). https://doi.org/10.1007/BF01716204

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  • DOI: https://doi.org/10.1007/BF01716204

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