Intrarenal atrial natriuretic peptide infusion lowers arterial pressure chronically

Chronic intravenous infusions of atrial natriuretic peptide (ANP) have been shown to lower mean arterial pressure (MAP) in both normal and hypertensive animals. However, the importance of the renal actions of ANP in mediating this hypotension is unknown. This study was designed to determine whether physiological or pathophysiological increases in intrarenal ANP levels influence long-term control of arterial pressure. ANP was infused into the renal artery of seven conscious, uninephrectomized, chronically instrumented dogs at 1, 2, and 4 ng · kg^-1 · min^-1 for 7 days at each dose, followed by a recovery period. Then ANP was infused intravenously following the same protocol. MAP decreased from 88 ± 3 to 78 ± 3 mmHg during intrarenal infusion of 1 ng · kg^-1 · min^-1 ANP; increasing the ANP infusion rate did not result in a further reduction in MAP. Systemic arterial plasma ANP concentration did not change from control (15 ± 5 pg/ml) during 1 or 2 ng · kg^-1 · min^-1 intrarenal ANP infusion but increased slightly during 4 ng · kg^-1 · min^-1 intrarenal ANP infusion, averaging 53 ± 11 pg/ml. Renal arterial plasma ANP concentrations were calculated to increase to ~ 120 ± 5, 248 ± 11, and 484 ± 22 pg/ml during 1, 2, and 4 ng · kg^-1 · min^-1 · min^-1 intrarenal ANP infusion, respectively. Intravenous ANP infusion did not alter MAP at 1 ng · kg^-1 · min^-1, but MAP was slightly lower than control during 2 and 4 ng · kg^-1 · min^-1 ANP infusion and remained below control during the postinfusion period. Systemic arterial plasma ANP concentrations increased from 42 ± 9 pg/ml during control to 68 ± 11 pg/ml during 1 ng · kg^-1 · min^-1 intravenous ANP infusion and further increased during 2 and 4 ng · kg^-1 · min^-1 ANP infusion, averaging 122 ± 9 and 177 ± 28 pg/ml, respectively. These results demonstrate that physiological increases in intrarenal ANP levels can lower arterial pressure chronically, independent of any systemic effects, and support the hypothesis that ANP controls arterial pressure through its intrarenal actions.