Programming of adult cardiovascular disease following exposure to late-gestation hyperglycemia.

BACKGROUND: In utero exposure to hyperglycemia is becoming increasingly prevalent as the number of women entering pregnancy with type II diabetes, or developing gestational diabetes, increases. Both animal studies and epidemiologic investigations have found cardiovascular abnormalities in adult offspring of hyperglycemic mothers (OHM). OBJECTIVE: We hypothesized that adult OHM would have abnormal cardiac function in vivo and increased susceptibility to ischemia. METHODS: Pregnant rats were made diabetic on day 12 of gestation. Serum glucose was monitored twice daily and insulin provided to maintain serum glucose at 200-400 mg/dl. Offspring were fostered to normal mothers after birth. Adult OHM were studied at 8-10 months of age with echocardiography to assess in vivo cardiac function and isolated hearts to determine the response to ischemia. RESULTS: Echocardiography found significant diastolic dysfunction in male OHM compared to male controls. In isolated hearts, baseline cardiac function and left ventricular compliance was significantly diminished in male OHM compared to controls. Ischemia caused a significant decline in heart function in controls and female OHM, while function in male OHM remained unchanged. CONCLUSIONS: Adult male OHM demonstrate programmed cardiac dysfunction. Given the growing number of pregnancies complicated by hyperglycemia, additional assessment of cardiac function of adults born to diabetic mothers may be warranted.

Localization of the renin-angiotensin system components to the skeletal muscle microcirculation.

OBJECTIVES: Local renin-angiotensin systems have been found in various organs and tissues throughout the body. The studies described here tested the hypothesis that a fully functional renin-angiotensin system exists in the skeletal muscle microvasculature. The purpose of this study was to localize the components and products of the system to the skeletal muscle microvasculature. METHODS: The presence of mRNA and protein for renin and angiotensinogen was shown by reverse transcriptase polymerase chain reaction analysis and immunohistochemistry, respectively. Angiotensin II concentration in isolated microvessels was measured by high-performance liquid chromatography separation and radioimmunoassay. RESULTS: Renin and angiotensinogen mRNA was detected from isolated cremaster microvessels. Specific staining for renin and angiotensinogen protein was found throughout the walls of microvessels. The concentration of the angiotensin II in the microvessels (104.3 +/- 18.1 fmol/g) was found to be higher than the concentration of angiotensin II in the plasma (8.7 +/- 1.2 fmol/mL) of the same animals. Also, it was shown that the microvessel angiotensin II concentrations in spontaneously hypertensive rats were higher than in Sprague-Dawley rats. CONCLUSIONS: The current study demonstrates that within the skeletal muscle microvessels, the components and products necessary for a local renin-angiotensin system are present, but does not rule out the possibility of interaction between circulating and tissue renin-angiotensin systems.