Effects of exogenous and endogenous natriuretic peptides on forearm vascular function in chronic heart failure.
OBJECTIVE
Natriuretic peptides (NPs) reduce central venous pressure in patients with chronic heart failure (cHF) despite attenuation of arterial, renal, and humoral effects. This suggests a preserved venodilator response. This study had 4 aims: to compare the venodilator effects of human NPs in patients with cHF; to assess the contribution of basal ANP and BNP levels to regulation of forearm vascular volume (FVV); to test the hypothesis that venous ANP responsiveness is preserved in cHF; and to assess the involvement of endothelial nitric oxide-synthase (eNOS) in NP-induced vascular effects.


RESULTS
Venous and arterial forearm vascular responses to incremental intra-arterial doses of ANP, Urodilatin, BNP, CNP, or the ANP receptor antagonist A71915 were studied in 53 patients and 11 controls. ANP receptor antagonism reduced FVV by 4.4%+/-1.2% (P<0.05). The forearm blood flow (FBF) response to ANP was significantly blunted in patients versus controls (P<0.01), whereas FVV increased similarly in both groups (maximum 14.7% and 13.4%, both P<0.001). The eNOS blockade reduced ANP-induced FBF changes in controls but not in patients (P<0.05), whereas similar reductions in FVV changes were seen in groups (both P<0.001).


CONCLUSIONS
In cHF venous, but not arterial, ANP responsiveness is preserved. Arterial endothelial dysfunction may contribute to NP resistance.
Wales Heart Research Institute, Cardiff, UK. matthschmitt@doctors.org.uk
Matthias
M
Schmitt
Prasad
P
Gunaruwan
Nicola
N
Payne
Justin
J
Taylor
Leong
L
Lee
Andrew J M
AJ
Broadley
Angus K
AK
Nightingale
John R
JR
Cockcroft
Allan D
AD
Struthers
John V
JV
Tyberg
Michael P
MP
Frenneaux
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001158:Arteries / Q000187:drug effects; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use; D002317:Cardiovascular Agents / Q000627:therapeutic use; D006152:Cyclic GMP / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D007269:Injections, Intra-Arterial; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology; D020098:Natriuretic Peptide, C-Type / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology; D045265:Natriuretic Peptides / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D052250:Nitric Oxide Synthase Type III; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014680:Veins / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology
D002317:Cardiovascular Agents; D004791:Enzyme Inhibitors; D045265:Natriuretic Peptides; D010446:Peptide Fragments; D044005:Tetrahydroisoquinolines; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; C078792:A 71915; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C056452:Ularitide; D009320:Atrial Natriuretic Factor; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP