Blunted renal response to atrial natriuretic peptide in congestive heart failure rats is reversed by the alpha 2-adrenergic agonist clonidine.
We wished to determine whether pharmacologic inhibition of the exaggerated sympathetic nerve activity in congestive heart failure (CHF) could restore the renal response to exogenous atrial natriuretic peptide (ANP) administration. Left ventricular (LV) myocardial infarction was induced in Sprague-Dawley rats (n = 16) by coronary artery ligature. Four to 6 weeks postoperatively, an isotonic saline (controls) or clonidine 5 micrograms/h infusion was given. Four hours later, all animals received incremental doses of rat ANP (99-126) (0.25, 0.5 and 1.0 microgram/kg/min). The continuous clonidine infusion transiently increased urinary volume (UV) as compared with the saline controls. Mean arterial pressure (MAP), heart rate (HR), and plasma norepinephrine (NE) were significantly decreased by clonidine. The graded ANP infusions significantly increased UV (saline 39.13 +/- 12.45 and clonidine 90.25 +/- 13.69 microliters/min, p less than 0.05) and UNaV (saline 4.26 +/- 1.10 and clonidine 8.81 +/- 1.59 mumol/min, p less than 0.05) in clonidine-pretreated rats as compared with saline-pretreated rats. We conclude that the diuretic and natriuretic responses to ANP are significantly increased in CHF after presynaptic inhibition of NE release by low-dose clonidine.
Feng
Q P
QP
Department of Clinical Pharmacology, Gothenburg University, Sweden.
Hedner
T
T
Hedner
J
J
Pettersson
A
A
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D006333:Heart Failure / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000294:innervation / Q000503:physiopathology; D008297:Male; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000652:urine; D013564:Sympathetic Nervous System / Q000187:drug effects
D009320:Atrial Natriuretic Factor; D012964:Sodium; D003000:Clonidine; D009638:Norepinephrine