Insulin mediated hemodynamic responses in spontaneous hypertensive rats (SHRs): effect of chromosome 4 gene transfer.
The spontaneous hypertensive rat (SHR) is a widely studied model of essential hypertension and has been reported to exhibit alterations in carbohydrate and lipid metabolism. Genetic linkage studies implicated that SHR carries deletion variant of Cd36 gene of chromosome 4, the gene that encodes fatty acid transporter. Thus it could be possible that primary genetic defect in SHR is compromised tissue utilization of fatty acid that would form the basis for the pathogenesis of hyperinsulinemia, insulin resistance and insulin-mediated responses. We measured both the hemodynamic and metabolic responses to insulin in SHR in comparison with the chromosome congenic spontaneous hypertensive rats (cSHRs) (rats in which piece of chromosome 4 containing wild type Cd36 was integrated into the SHR genome). A bolus infusion of insulin increased iliac conductance and decreased blood pressure in Wistar Kyoto (WKY) rats. However, in SHR insulin did not reduce blood pressure as in WKY but after about 15 min it significantly enhanced blood pressure and reduced iliac conductance. Whereas in cSHR insulin did not reduce blood pressure as in WKY rats. However, pressor responses to insulin were eliminated by chromosome 4 gene transfer. Glucose clearance was significantly slower in both SHR and cSHR. Glucose tolerance test revealed that SHR are hyperinsulinemic and insulin resistant. These findings indicate that transfer of segment of chromosome 4 from Brown Norway rats onto spontaneous hypertensive background eliminates hyperinsulinemia and pressor effects of insulin.
Rao
Sumangala P
SP
Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan 48201-1928, USA
McRae
Crystal
C
Lapanowski
Karen
K
Churchill
Monique
M
Kurtz
Theodore W
TW
Dunbar
Joseph C
JC
D000818:Animals; D001786:Blood Glucose; D001794:Blood Pressure / Q000187:drug effects*; D018955:CD36 Antigens / Q000235:genetics*; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D005951:Glucose Tolerance Test; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000235:genetics*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D001786:Blood Glucose; D018955:CD36 Antigens; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D007328:Insulin