Hypertension plus diabetes mimics the cardiomyopathy induced by nitric oxide inhibition in rats.
OBJECTIVE
We compared the myocardial lesions caused by the long-term inhibition of nitric oxide (NO) biosynthesis with those associated with renovascular hypertension (two-kidney, one-clip model [2K-1C]) and superimposed streptozotocin-induced diabetes mellitus (DM).


METHODS
Prospective trial.


METHODS
University laboratory.


METHODS
Male Wistar rats were classified into the following groups: (1) a control group; (2) the L-NAME group (treatment with the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester [L-NAME], 75 micro mol per rat per day, orally); (3) the 2K-1C group (renovascular hypertension); (4) the DM group (treatment with streptozotocin, 60 mg/kg via intraperitoneal route); and (5) the 2K-1C plus DM group (renovascular hypertension and streptozotocin-induced DM). Arterial BP was measured by a tail-cuff method for 3 weeks, after which histologic and stereological analysis of the heart was done and cardiac NO synthase type 3 (NOS3) levels were assessed by Western blotting. The circulating levels of nitrates/nitrites and thromboxane B(2) (TXB(2), the stable metabolite of thromboxane A(2)) were also measured.


RESULTS
In DM and 2K-1C rats, the myocardial lesions consisted mainly of recent myocardial infarcts, which were more severe in the 2K-1C plus DM group. In L-NAME-treated rats, multiple foci of reparative fibrosis and fresh myocardial necrosis resembled the severe lesions found in the 2K-1C plus DM group. Although NOS3 protein expression increased (19 to 44%; p < 0.05) in all treated groups, serum nitrate/nitrite levels decreased only in the L-NAME group and the 2K-1C plus DM group. These two groups also showed a more pronounced increase in TXB(2) concentrations.


CONCLUSIONS
These results indicate that the association of hypertension and DM mimics the alterations induced by L-NAME in rats, which suggests a role for NO in the pathophysiology of hypertensive-diabetic cardiomyopathy.
Sampaio
Rita C
RC
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, Brazil 14049-900.
Tanus-Santos
Jose E
JE
Melo
Silvia E S F C
SE
Hyslop
Stephen
S
Franchini
Kleber G
KG
Luca
Iara M
IM
Moreno
Heitor
H
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002312:Cardiomyopathy, Hypertrophic / Q000209:etiology* / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004195:Disease Models, Animal; D006978:Hypertension, Renovascular / Q000150:complications*; D007150:Immunohistochemistry; D008297:Male; D009206:Myocardium / Q000473:pathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000096:biosynthesis*; D009929:Organ Size; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000494:pharmacology
D009569:Nitric Oxide; D013311:Streptozocin; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester