Blunted effect of ANP on hematocrit and plasma volume in streptozotocin-induced diabetes mellitus in rats.
Atrial natriuretic peptide (ANP) infusion increases hematocrit and decreases plasma volume by inducing a transfer of plasma fluid from the vascular to the interstitial compartment. Diabetes mellitus is associated with resistance to the renal actions of ANP. We explored the possibility that the extrarenal responses to ANP may also be altered in the diabetic state by measuring changes in arterial pressure and hematocrit during infusion of ANP (1 microgram.kg-1 x min-1 for 45 min) into anesthetized, acutely nephrectomized rats 2-3 wk after induction of diabetes from intravenous streptozotocin (STZ) injection (60 mg/kg). Blood glucose was significantly elevated in diabetic rats when compared with control and insulin-treated diabetic rats. Arterial pressure during ANP infusion decreased similarly in control; diabetic, and insulin-treated diabetic rats (by 7.6 +/- 1.6, 9.6 +/- 1.9, and 8.2 +/- 2% respectively; all P < 0.002). In control rats, hematocrit increased progressively to a maximum value of 9.5 +/- 0.9% as a result of the infusion, corresponding to a decrease in plasma volume of 16.3 +/- 1.3%. In contrast, the ANP-induced increase in hematocrit was markedly blunted in diabetic rats (1.6 +/- 0.8%; P < 0.0001 vs. ANP infusion in control rats). Reducing the hyperglycemia in diabetic rats by insulin therapy restored the increase in hematocrit in response to ANP (8.5 +/- 1.1%; P < 0.0001 vs. ANP infusion in diabetic rats and P = NS vs. control rats). ANP infusion increased plasma ANP levels to the same extent in the three groups, whereas plasma guanosine 3',5'-cyclic monophosphate (cGMP) was significantly less in diabetic as compared with control and insulin-treated diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Valentin
J P
JP
Division of Nephrology, San Francisco General Hospital, University of California San Francisco 94110.
Sechi
L A
LA
Humphreys
M H
MH
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001798:Blood Proteins / Q000378:metabolism; D001810:Blood Volume / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D006152:Cyclic GMP / Q000097:blood / Q000652:urine; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000503:physiopathology / Q000652:urine; D015309:Glucose Clamp Technique; D006400:Hematocrit; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007700:Kinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D013997:Time Factors
D001786:Blood Glucose; D001798:Blood Proteins; D007328:Insulin; D011994:Recombinant Proteins; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP