Salt-sensitive hypertension in ANP knockout mice: potential role of abnormal plasma renin activity
| Autor: | Stephen C. Pang, Harald Sonnenberg, Luis G. Melo, C. K. Chong, T. G. Flynn, A. T. Veress |
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| Rok vydání: | 1998 |
| Předmět: |
Male
Heterozygote medicine.medical_specialty Nitric Oxide Synthase Type III Physiology Nitric Oxide Synthase Type II Blood Pressure Peptide hormone Kidney Mice chemistry.chemical_compound Atrial natriuretic peptide Physiology (medical) Internal medicine Renin Renin–angiotensin system medicine Animals Protein Precursors Mice Knockout Analysis of Variance Aldosterone Endothelin-1 Chemistry Myocardium Homozygote Kidney metabolism Sodium Dietary Exons Diet Sodium-Restricted Endothelin 1 Endocrinology Blood pressure Hypertension Knockout mouse Female Angiotensin I Nitric Oxide Synthase Atrial Natriuretic Factor |
| Zdroj: | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 274:R255-R261 |
| ISSN: | 1522-1490 0363-6119 |
| DOI: | 10.1152/ajpregu.1998.274.1.r255 |
| Popis: | Atrial natriuretic peptide (ANP), a peptide hormone produced by the heart, exerts a chronic hypotensive effect. Knockout mice with a homozygous disruption of the pro-ANP gene (−/−) are incapable of producing ANP and are hypertensive relative to their wild-type (+/+) siblings. Previous studies showed that arterial blood pressure (ABP) was further increased in conscious −/− mice kept for 2 wk on 2% salt, but not in anesthetized −/− mice after 1 wk on 8% salt. To determine whether inconsistencies in observed effects of salt on ABP of −/− mice are due to duration of increased salt intake and/or the state of consciousness of the animals, we measured ABP from an exteriorized carotid catheter during and after recovery from anesthesia with ketamine-xylazine in adult +/+ and −/− mice kept on low (LS; 0.008% NaCl)- or high (HS; 8% NaCl)-salt diets for 3–4 wk. Conscious ABP ± SE (mmHg) of +/+ mice did not differ significantly on either diet (HS, 113 ± 3; LS, 110 ± 5). However, on HS diet −/− mice had significantly higher ABP (135 ± 3; P < 0.001) than both −/− (115 ± 2) and +/+ (110 ± 5) mice on LS diet. Anesthesia decreased ABP in all groups, but the genotype- and diet-related differences were preserved. Plasma renin activity (PRA, ng ANG I ⋅ ml−1 ⋅ h−1) in blood collected at termination of experiment was appropriately different on the 2 diets in +/+ mice (HS, 4.9 ± 1.9; LS, 21 ± 2.8). However, PRA failed to decrease in −/− mice on HS diet (HS, 18 ± 2.9; LS, 19 ± 3.7). Independent of genotype, concentration of endothelin-1 (ET-1, pg/mg protein) and endothelial constitutive NOS (ecNOS, density/100 μg protein) was significantly elevated in kidneys of mice fed on HS diet (ET-1 −/−, 31 ± 4.7 and +/+, 32 ± 4.1; ecNOS −/−, 160 ± 19 and +/+, 156 ± 19) compared with mice fed on LS diet (ET-1 −/−, 19 ± 1.9 and +/+, 21 ± 1.8; ecNOS −/−, 109 ± 13 and +/+, 112 ± 18). We conclude that, regardless of the state of alertness, −/− mice develop salt-sensitive hypertension after prolonged feeding on HS, in part due to their inability to reduce PRA, whereas the specific renal upregulation of ecNOS and ET-1 in response to HS intake may be an ANP-independent adaptive adjustment aimed at improving kidney function and counteracting the pressor effect of salt. |
| Databáze: | OpenAIRE |
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