Natriuretic and vasodilating activities of intrarenally administered atriopeptin II, substance P and bradykinin in the dog.
The mechanism of the diuretic effect of atrial natriuretic factor is unclear. In this study, we compared the renal vasodilating and diuretic effects of renal arterial infusions of rat atriopeptin II in anesthetized dogs to see if natriuresis and increases in total renal blood flow were associated. The vasodilators substance P and bradykinin also were tested. Volume (V), Na+ and K+ concentration and Na+ and K+ content (UNaV; UkV) of urine from the infused and contralateral kidneys (IK; CK) were measured as well as mean total renal blood flow (RBF) of the IK. Atriopeptin II (30-1000 ng/kg/min) slightly promoted RBF by up to 20%, but raised V, UNaV and UkV by a maximum of 79, 190 and 100%, respectively. Substance P (0.01-30 ng/kg/min) raised RBF of IK by a maximum of 59%, reduced mean blood pressure by 26% and had a biphasic effect on IK excretion: V, UNaV and UkV were increased maximally by 105, 154 and 42% at 1.0 ng/kg/min, whereas progressively less diuresis, natriuresis and kaliuresis occurred at higher (hypotensive) doses. CK excretion was unchanged. Bradykinin (1-100 ng/kg/min) raised RBF, V, UNaV, and UkV of IKs by a mean maximum of 97, 70, 201 and 47%, respectively, with no changes in mean blood pressure or CK excretion. The natriuretic and hyperemic effects of nonhypotensive doses of each peptide were significantly correlated. However, atriopeptin II uniquely promoted Na+ excretion, but not RBF at the lowest dose tested, and, after 10 min washout of the 1000-ng/kg/min dose, and did not appreciably promote RBF after 10 min of infusion. It also caused CK diuresis.(ABSTRACT TRUNCATED AT 250 WORDS)
DeFelice
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AF
Sterling-Winthrop Research Institute, Department of Pharmacology, Rensselaer, New York.
Brousseau
A
A
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006852:Hydrochlorothiazide / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D013373:Substance P / Q000494:pharmacology*; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D006852:Hydrochlorothiazide; D013373:Substance P; D009320:Atrial Natriuretic Factor; D001920:Bradykinin