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Fetal Physiological Programming
1Nephrology Department, Federal University of São Paulo-UNIFESP, São Paulo, Brazil; 2Hypertension Unit and Heart Institute of Medical School-University of São Paulo, São Paulo, Brazil; 3Wright State University School of Medicine, Department of Pharmacology & Toxicology, Dayton, Ohio; and 4University of São Paulo, Department of Anatomy, São Paulo, Brazil
Submitted 1 June 2004 ; accepted in final form 10 January 2005
Studies were conducted in rats to determine the effect of maternal diabetes and the consequent hyperglycemia on cardiovascular function in the offspring. Diabetes was induced in pregnant Wistar rats through streptozotocin injection (50 mg/kg). Cardiovascular parameters were measured in 2-mo-old offspring animals of diabetic (OD, n = 12) and control rats (OC, n = 8). Arterial pressure (AP), heart rate (HR), baroreflex sensitivity, and vascular responsiveness to phenylephrine (PH) and sodium nitroprusside (SN) were measured. Angiotensin-converting enzyme (ACE) activity in heart, kidney, and lung was determined. OD rats exhibited increases in systolic AP (138 ± 8 vs. 119 ± 6 mmHg, OD vs. OC), with no change in HR (342 ± 21 vs. 364 ± 39 beats per minute (bpm), OD vs. OC). The reflex tachycardia elicited by SN was reduced in OD rats, as indicated by the slope of the linear regression (2.2 ± 0.4 vs. 3.6 ± 0.8 bpm/mmHg, OD vs. OC). Vascular responsiveness to PH was increased 63% in OD rats compared with OC. OD rats showed increases in ACE activity in heart, kidney, and lung (1.13 ± 0.24, 3.04 ± 0.86, 40.8 ± 8.9 vs. 0.73 ± 0.19, 1.7 ± 0.45, 28.1 ± 6 nmol His-Leu·min1 mg protein1, OD vs. OC). Results suggest that diabetes during pregnancy affects cardiovascular function in offspring, seen as hypertension, baroreflex dysfunction, and activation of tissue renin-angiotensin system.
cardiovascular; heart rate; development; angiotensin-converting enzyme; renin-angiotensin system; hyperglycemia
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