Hepatocyte growth factor (HGF) is an index of arteriosclerosis in hypertensive patients. Correlation to pulse wave velocity (PWV) and serum HGF concentration

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POSTERS: Experimental Hypertension

P-322 EFFECT OF LOSARTAN ON OXIDATIVE STRESSINDUCED HYPERTENSION IN SPRAGUE-DAWLEY RATS Mohamed A. Bayorh, Agaba A. Ganafa, Robin R. Socci, Danita E. Eatman, Imad Abukhalaf, Natalia Silvestrov, Nerimiah L. Emmett. 1 Pharmacology, Morehouse School of Medicine, Atlanta, GA, United States Hypertension induced by chronic oxidative stress has been demonstrated in normal rats and in situations of normal or low plasma angiotensin. In the current study, we investigated the effect of the AT1 receptor blocker losartan (LOS, 10 mmol/kg/day p.o.) on oxidative stress, induced by glutathione (GSH) depletion (using buthionine sulfoximine, BSO, 30 mmol/L/day in the drinking water), in Sprague-Dawley rats. The control animals received regular drug-free drinking water. We measured the blood pressure by tail-cuff plethysmography and determined the levels of plasma 8-isoprostane (ISO), nitric oxide (NO), prostacyclin (PGI2) and thromboxane A2 (TXA2) by enzyme immunoassay, and plasma and heart tissue GSH by HPLC. Blood pressure (BP), ISO and TXA2 were significantly elevated; whereas NO, PGI2 and GSH were significantly reduced in the BSO-treated group compared to controls. Losartan significantly reduced the BSO-induced elevation of BP and TXA2, but did not change the plasma levels of NO, PGI2 and ISO. Thus, oxidative stress-induced hypertension is due to a dysfunction of the endothelium. In addition, this hypertensive response involves increases in thromboxane A2 levels and AT1 receptor activity. Supported in part by NIH grants S06GM08248-12 (M.A.B.) and P20RR11104-06 (I.A.). Key Words: oxidative stress, hypertension, losartan

P-323 EFFECT OF HIGH GLUCOSE INTAKE AND INSULIN RESISTANCE ON OXIDATIVE STRESS AND ARTERIAL PRESSURE IN THE RAT Adil El Midaoui, Rong Wu, Jacques De Champlain. 1Physiology, Universite´ de Montre´al, Montreal, QC, Canada This study was designed to assess the impact of high glucose intake on arterial pressure in correlation with the degree of oxidative stress. The insulin resistance was induced by the addition of 10 % glucose to drinking water of 240 gr Sprague Dawley rats during three weeks. The oxidative stress was evaluated by measuring the superoxide anion production using the lucigenin enhanced chemiluminescence method in the aorta. The antioxidant reserve was assessed by measuring the activity of glutathione peroxidase (GPx) spectrophotometrically in red blood cells and plasma. The chronic administration of glucose resulted in 73% increase in glycemia (7.6 ⫾ 0.9 mM vs 4.4 ⫾ 0.1 mM, P⬍0.01) and 100 % increase in insulinemia (1039 ⫾ 177 pM vs 519 ⫾ 94 pM, P⬍0.05) . The chronic glucose feeding also resulted in an increase of 52 % (4497 ⫾ 453 cpm/min/mg vs 2953 ⫾ 113 cpm/min/mg, P⬍0.01) in basal superoxide anion production in aorta. This regimen had no effect on the activity of GPx in the red blood cells but resulted in a decrease of 16 % (158 ⫾ 8 mU/ml vs 189 ⫾ 7 mU/ml, P⬍0.05) in the activity of GPx in plasma. The high glucose intake was also associated with a progressive increase in systolic arterial pressure which reached 166 mmHg after three weeks of this regimen (P⬍0.001). Positive correlations were observed between the superoxide anion production and the arterial pressure (r⫽0.599; P⬍0.02) or glucose levels (r⫽0.662; P⬍0.01). These results suggest that the rise in blood pressure associated to hyperinsulinemia may be explained in part by an increase in oxidative stress characterized by an enhancement in the production of superoxide anion in the aorta and a reduction in the activity of GPx in the plasma. This phenomenon could

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explain the association which seems to exist between insulin resistance and hypertension. Key Words: Diabetes, Hypertension, oxidative stress

P-324 AN EXPERIMENTAL ACUTE ANGIOTENSINMEDIATED RENAL HYPERTENSION IN THE RAT Giorgio Recordati, Federica Zorzoli, Olivia Pontara, Alberto Zanchetti. 1Centro di Fisiologia Clinica ed Ipertensione, Universita’ di Milano, Milano, Italy In a previous communication (Am J Hypert, 13 (4, part 2): 273A, 2000) we have reported that the experimental acute renal hypertension (EARH) which follows the reopening (REOP) of the right renal hilum after a period of complete renal ischaemia (functional right nephrectomy: FRN) was present only in rats nephrectomized on the controlateral side. The present report modifies our previous conclusion showing that the EARH is also present in rats with the controlateral left kidney intact. Blood pressure (BP), heart rate (HR), rate of breathing (RB), rectal temperature (T), urine flow rate, osmolality and Na⫹, K⫹ excretion from the right kidney were continuously monitored for one hour before, during FRN, and for one hour after REOP in pentobarbital anaesthetized, spontaneously breathing Sprague- Dawley (250-300g) rats with the left kidney intact (group 1) and in rats nephrectomized on the left side (group 2). In group 1 the REOP after a FRN of 30 (group 1a, n⫽5), 60 (group 1b, n⫽5), 180 (group 1c, n⫽5) min was followed by an average peak increase of 12.4 ⫾ 2.7, 3.5 ⫾ 1.2 and 47.5 ⫾ 4.4 mmHg (mean ⫾ S.E.) in systolic BP (SBP) respectively, and it was highly reproducible for FRN of 180 min only. In group 2 the REOP of the only remaining and completely ischaemic right kidney after 30 (group 2a, n⫽5), 60 (group 2b, n⫽5) and 180 (group 2c, n⫽5) min of FRN was followed by an average peak increase of 19.4 ⫾ 4.3, 36.1 ⫾ 11.0 and 72.8 ⫾ 10.5 mmHg in SBP respectively. A marked tachycardia was observed in group 2c only. The i.v. injection of 3 mg/Kg of Irbesartan 30 min before REOP in 3 additional rats of group 2b, completely prevented the acute increase of BP observed in this group of rats. Plasma renin activity (PRA) measured 1 hour after REOP, was directly related to the duration of FRN, being maximal in group 1c and 2c, 63.9 ⫾ 5 .9 and 57.5 ⫾ 7.7 ng AI/ml/hr respectively. These data indicate that the EARH which follows the REOP of a completely ischaemic kidney is present either in rats with the controlateral kidney intact and in rats previously nephrectomized on the left side. Together with the effects of Captopril, the response to Irbesartan indicates that EARH is due to an acute release of renin and conseguent formation of angiotensin II, and thus it represents an useful experimental model of an acute angiotensin-mediated renal hypertension (J. Hypert 18:1277, 2000). Key Words: Acute renin release, Renal ischaemia, Functional right nephrectomy

P-325 HEPATOCYTE GROWTH FACTOR (HGF) IS AN INDEX OF ARTERIOSCLEROSIS IN HYPERTENSIVE PATIENTS. CORRELATION TO PULSE WAVE VELOCITY (PWV) AND SERUM HGF CONCENTRATION Keiko Matsumoto, Ryuichi Morishita, Norio Komai, Michael L. Tuck, Toshio Ogihara. 1Department of Geriatric Medicine, Osaka University Medical School, Suita, Osaka, Japan, 2Department of Medicine, UCLA School of Medicine, Los Angeles, CA, United States HGF has many organ protective functions. Our previous data demonstrated that HGF stimulated growth of endothelial and epithelial cells in vitro. Moreover, Ang II and TGF-b significantly decreased local HGF production in endothelial cells. Therefore, we examined the clinical effects of an ACE inhibitor (cilazapril) and ␤-blocker (atenolol) on

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hypertensive patients. An ACE inhibitor (cilazapril; 0.5or1.0mg/day) and ␤-blocker (atenolol; 50or 100mg/day) were administrated to agematched hypertensive patients for 6 months. Male are 9 and female are 6 persons. All hypotensive drugs were leaved off before trials were stated over 3 months. PWV were measured left carotid and femoral artery by FCP-4731 FUKUDA DENSHI. Serum HGF concentrations were measured by EIA. This study demonstrated that HGF prevented arteriosclerosis. Systolic and diastolic Blood pressure were significantly decreased in cilazapril and atenolol treated groups equally(p⬍0.01). Moreover, cilazapril significantly was improved PWV and serum HGF concentra-

POSTERS: Experimental Hypertension

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tion. (p⬍0.01) Of importance, serum HGF production was markedly increased by only cilazapril treatment. Together with a significant improved PWV by cilazapril. The present data demonstrated the regression arteriosclerosis and increased serum HGF production by cilazapril in hypertensive patient. Protective actions of cilazapril on arterial epithelial formation may be partially mediated by increased serum HGF production. Key Words: Hepatocyte Growth Factor, ACE inhibitor, Primary Hypertension