Cardiovascular kinin-generating capability in hypertensive fructose-fed rats.
OBJECTIVE
The hypertensive state is often associated with metabolic abnormalities, including glucose intolerance. Tissue kallikrein, a potent kinin-generating enzyme, is present in the vascular wall and heart tissue. High dietary fructose consumption is reported to induce hyperinsulinemia, hypertriglyceridemia and hypertension. The objective of the present study was to examine the status of kallikrein in vascular and cardiac tissue from highly fructose-fed rats and to delineate the effect of kinins and the angiotensin converting enzyme inhibitor ramipril in this animal model of glucose intolerance.


METHODS
Male Wistar rats (350 g body weight) were divided into four groups of 10 rats each: (1) controls; (2) oral ramipril at 500 microg/kg per day for the last 2 study weeks; (3) fructose in drinking water as a 10% (w/v) solution for 4 weeks; and (4) fructose + ramipril, with fructose administered as in group 3 plus the administration of ramipril for the last 2 study weeks. Systolic blood pressure (tail-cuff method), glucose tolerance (2 g/kg body weight intraperitoneally) and metabolic parameters were recorded. Kallikrein activity in tail artery and heart tissue homogenates was estimated at the end of the 4th study week from measurements of kininogenase activity and kinins generated by a radioimmunoassay.


RESULTS
The area under the curve for the glucose tolerance test increased from 1265 +/- 103 mmol/l after 120 min in the control and 1152 +/- 36 mmol/l in the ramipril group (NS) to 2628 +/- 143 mmol/l in the fructose group (P<0.01). The administration of ramipril to fructose-treated rats in group 4 improved glucose tolerance (2160 +/- 100 mmol/l; P<0.05 versus group 3). Blood pressure increased significantly in fructose-fed rats but fell markedly in fructose-fed rats treated with ramipril (P<0.01). Kallikrein activity measured in the heart and vessels increased as a consequence of fructose administration (P<0.05), but the administration of ramipril increased this parameter to a much greater extent (P<0.01 versus control group), which correlated closely with the decrease in blood pressure and the improvement in glucose tolerance observed in the fructose + ramipril group.


CONCLUSIONS
The administration of fructose as a solution in the drinking water induced glucose intolerance and increased blood pressure. Treatment with the angiotensin converting enzyme inhibitor ramipril improved glucose tolerance and significantly diminished blood pressure. Cardiovascular kinin-generating capability increased in treated animals and this increase was even higher when rats were treated with ramipril, suggesting that kinins, acting as a paracrine hormonal system, can exert cardiovascular protection and contribute to the beneficial effects of angiotensin converting enzyme inhibitor.
Miatello
R M
RM
Laboratory of Experimental Hypertension and Vasoactive Substances, School of Medicine and National Council of Research (CONICET), Mendoza, Argentina. rmiatell@fmed2.uncu.edu.ar
Damiani
M T
MT
Nolly
H L
HL
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001158:Arteries / Q000201:enzymology; D001794:Blood Pressure / Q000502:physiology; D002319:Cardiovascular System / Q000378:metabolism*; D004032:Diet; D005632:Fructose / Q000008:administration & dosage* / Q000494:pharmacology; D005951:Glucose Tolerance Test; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007610:Kallikreins / Q000378:metabolism; D007705:Kinins / Q000096:biosynthesis*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D017257:Ramipril / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000959:Antihypertensive Agents; D007705:Kinins; D005632:Fructose; D007610:Kallikreins; D017257:Ramipril