Biological actions of brain natriuretic peptide in thoracic inferior vena caval constriction.
Brain natriuretic peptide (BNP) shares structural and functional similarities to atrial natriuretic peptide (ANP). Although BNP and ANP interact with the same biologically active guanylate cyclase-coupled receptor, recent reports conflict with regard to the biological actions of exogenous BNP in sodium-retaining and edematous states. We studied the biological actions of BNP in normal dogs (n = 5) and sodium-avid dogs with chronic thoracic inferior vena caval constriction (TIVCC) (n = 6). In normal dogs BNP increased glomerular filtration rate, renal blood flow, and urinary sodium excretion and decreased proximal and distal fractional reabsorption of sodium with activation of urinary guanosine 3',5'-cyclic monophosphate (cGMP). These renal actions occurred in association with marked hypotensive actions and activation of systemic cGMP. In TIVCC, a state characterized by chronic reductions of cardiac output, avid sodium retention, edema, and activation of the renin-angiotensin-aldosterone system (RAAS), the renal actions of BNP were absent in association with marked attenuation of the urinary cGMP response. In contrast, an enhanced hypotensive response with preserved activation of systemic cGMP was observed. In neither normal dogs nor TIVCC dogs did BNP inhibit the RAAS. These studies report that BNP is a potent vasoactive and natriuretic peptide with potent proximal and distal tubular actions in normal dogs. These studies also demonstrate that in TIVCC, a model of low cardiac output and congestive failure that results in marked sodium retention with edema in which there is activation of the RAAS, the renal actions of BNP are attenuated while the vasoactive actions are enhanced.
Clavell
A L
AL
Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905.
Stingo
A J
AJ
Aarhus
L L
LL
Burnett
J C
JC
D000042:Absorption; D000818:Animals; D002303:Cardiac Output, Low / Q000503:physiopathology*; D002319:Cardiovascular System / Q000187:drug effects; D003250:Constriction; D006152:Cyclic GMP / Q000378:metabolism; D004285:Dogs; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006333:Heart Failure / Q000503:physiopathology*; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000493:pharmacokinetics; D013909:Thorax; D014682:Vena Cava, Inferior / Q000502:physiology
D009419:Nerve Tissue Proteins; D020097:Natriuretic Peptide, Brain; D012964:Sodium; D006152:Cyclic GMP