Blood pressure, cardiac, and renal responses to salt and deoxycorticosterone acetate in mice: role of Renin genes
| Autor: | Michel Burnier, Jürg Nussberger, Giulio Gabbiani, Hans R. Brunner, Edith Hummler, Qing Wang, Sophie Clément |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2002 |
| Předmět: |
medicine.medical_specialty
medicine.drug_class Sodium Chloride/pharmacology Blood Pressure Cardiomegaly Sodium Chloride Biology ddc:616.07 Receptors Angiotensin/physiology Kidney Plasma renin activity Losartan Blood Pressure/drug effects Receptor Angiotensin Type 1 Muscle hypertrophy Mice Losartan/pharmacology Internal medicine Renin Renin–angiotensin system medicine Animals Cardiomegaly/chemically induced Desoxycorticosterone Receptor Receptors Angiotensin Hyperplasia General Medicine Renin/genetics Receptor antagonist Desoxycorticosterone/pharmacology Angiotensin II Mice Inbred C57BL medicine.anatomical_structure Endocrinology Nephrology Kidney/drug effects/pathology medicine.drug |
| Zdroj: | Journal of the American Society of Nephrology, Vol. 13, No 6 (2002) pp. 1509-1516 |
| ISSN: | 1046-6673 |
| Popis: | Several studies have demonstrated that mice are polymorphic for the number of renin genes, with some inbred strains harboring one gene (Ren-1(c)) and other strains containing two genes (Ren-1(d) and Ren-2). In this study, the effects of 1% salt and deoxycorticosterone acetate (DOCA)/salt were investigated in one- and two-renin gene mice, for elucidation of the role of renin in the modulation of BP, cardiac, and renal responses to salt and DOCA. The results demonstrated that, under baseline conditions, mice with two renin genes exhibited 10-fold higher plasma renin activity, 100-fold higher plasma renin concentrations, elevated BP (which was angiotensin II-dependent), and an increased cardiac weight index, compared with one-renin gene mice (all P < 0.01). The presence of two renin genes markedly increased the BP, cardiac, and renal responses to salt. The number of renin genes also modulated the responses to DOCA/salt. In one-renin gene mice, DOCA/salt induced significant renal and cardiac hypertrophy (P < 0.01) even in the absence of any increase in BP. Treatment with losartan, an angiotensin II AT(1) receptor antagonist, decreased BP in two-renin gene mice but not in one-renin gene mice. However, losartan prevented the development of cardiac hypertrophy in both groups of mice. In conclusion, these data demonstrate that renin genes are important determinants of BP and of the responses to salt and DOCA in mice. The results confirm that the Ren-2 gene, which controls renin production mainly in the submaxillary gland, is physiologically active in mice and is not subject to the usual negative feedback control. Finally, these data provide further evidence that mineralocorticoids promote cardiac hypertrophy even in the absence of BP changes. This hypertrophic process is mediated in part by the activation of angiotensin II AT(1) receptors. |
| Databáze: | OpenAIRE |
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