Reduction of nitric oxide availability is responsible for altered endothelium-dependent vasodilation in the radial artery of hypertensive patients

AJH–April 2002–VOL. 15, NO. 4, PART 2

available. To seek an effective treatment (Rx) time, rats were randomly assigned into control or Rx groups with each subgroup of 5 rats and Epo was given at 0, 4, 8, 12, 16 and 20 hours in each assigned group. BP, Hct and BW were measured just before and immediately after the completion of a 4-week course of twice weekly Epo (20-U/kg BW) or physiological saline injections. Intra-arterial BP was measured using the rat’s femoral artery. Before Rx, the inter-group differences for BP, BW and Hct in Epo vs. saline Rx groups were not statistically significant (SS). BW was lowered by Epo overall. Epo Rx increased Hct markedly overall and at each of the 6 test times, all p⬍0.0001, and splenomegaly characterized each rat. An increase in BP was detected at 8, 12, 16 and 20 hours, but not at 00 or 04 hours. Circadian BPs in saline control vs. Rx groups are as follow: 89⫾3.4 vs. 86⫾2.8 for before Rx, p⬍ns; 116⫾1.7 vs. 135⫾2.6 for post-Rx, p⬍0.0001. Furthermore, the Rx group had markedly increased amplitude when compared with the saline group, 48.7 vs. 27.2, p⬍0.0001. Thus, the time of the Epo Rx may be important. Epo dose should be reevaluated to prevent further organ damage, including the spleen. Since Epo stimulates endothelin, characterized by prominent extracircadian components, the broader circadian optimization of Epo effects is indicated. Key Words: Erythropoietin, Angiogenesis, Circadian Blood Pressure

P-272 PLASMA TOTAL CHOLESTEROL ENHANCES ENDOTHELIAL DYSFUNCTION IN ESSENTIAL HYPERTENSIVE PATIENTS Isabella Sudano, Daniele Versari, Guido Salvetti, Isabella Kardasz, Lorenzo Ghiadoni, Armando Magagna, Stefano Taddei, Antonio Salvetti. Internal Medicine, University of Pisa, Pisa, Italy. Essential hypertension (EH) and hypercholesterolemia (HC) are characterised by impaired endothelium(END)-dependent vasodilation (VD). In this study we assessed whether an alteration in lipid profile can determine an additive effect on impaired endothelial function in the peripheral microcirculation of (EH) patients. We studied n⫽199 EH patients divided in three groups according to total cholesterol (TC) plasma levels and n⫽40 normotensive and normocholesterolemic subjects. Normal (n⫽40, 37 males, age 51.2⫾9.3 yrs, BP 124.4⫾6.8/80.7⫾5.6 mmHg, TC 181.6⫾18.7 mg/dl, HDL 53.3⫾12.4 mg/dl, LDL 108.2⫾15.0 mg/dl); Group 1 (n⫽ 70, 63 males, age 49.2⫾10.2 yrs, BP 151.5⫾8.2/ 98.5⫾4.5 mmHg, TC 178.8⫾19.2 mg/dl, HDL 48.2⫾9.7 mg/dl, LDL 108.3⫾18 mg/dl); Group 2 (n⫽ 90, 81 males, age 50.1⫾8.3 yrs, BP 152.6⫾11.3/98.9⫾5.0 mmHg, TC 218.8⫾11.7 mg/dl, HDL 46.1⫾12 mg/dl, LDL 143.5⫾15.4 mg/dl) Group 3 (n⫽ 39, 35 males, age 52.7⫾8.4 yrs, BP 153.3⫾10.9/99.4⫾4.4 mmHg, TC 259.9⫾14.4 mg/dl, HDL 49.3⫾10.7 mg/dl, LDL 169.8⫾17.6 mg/dl). All the study subgroups were comparable for glucidic profile (within normal range) and smoking history. We measured the forearm blood flow (FBF, strain-gauge venous plethysmography) changes induced by intrabrachial infusion of acetylcholine (ACH, from 0.15 to 15␮g/100 ml/min) and sodium nitroprusside (SNP from 1 to 4 ␮g/100 ml/min), an END-dependent and -independent vasodilator, respectively. VD to ACH resulted to be reduced in EH patients with low TC (group 1) as compared to controls (normal subjects from 3.0⫾0.6 to 19.2⫾4.1 ml/100 ml/min, group 1 from 3.1⫾0.6 to 17.5⫾5.0 ml/100 ml/min; p⬍0.01 vs normal subjects). Moreover the response to ACH showed a further reduction in group 2 as compared to group 1 (from 3.1⫾0.6 to 15.6⫾5.7 ml/100 ml/min; p⬍0.01), and in group 3 (from 3.0⫾0.6 to 13.2⫾6.0 ml/100 ml/min) as compared to group 1 (p⬍0.01) and group 2 (p⬍0.01). In contrast the VD to SNP was not different in healthy controls

POSTERS: Endothelial Factors

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and in the three subgroups (FBF: normal subjects from 3.1⫾0.5 to 15.6⫾4.0 group 1 from 3.2⫾0.5 to 16.1⫾5.7; group 2 from 3.2⫾0.6 to 15.3⫾5.2; group 3 from 3.2⫾1.2 to 14.8⫾5.0; p: n.s.). This study indicates that in EH patients characterised by the presence of endothelial dysfunction plasma TC can exert a further negative effect on END-dependent VD. Key Words: Endothelium, Essential Hypertension, Plasma Cholesterol

P-273 REDUCTION OF NITRIC OXIDE AVAILABILITY IS RESPONSIBLE FOR ALTERED ENDOTHELIUMDEPENDENT VASODILATION IN THE RADIAL ARTERY OF HYPERTENSIVE PATIENTS Lorenzo Ghiadoni, Isabella Kardasz, Armando Magagna, Daniele Versari, Simona Buralli, Guido Salvetti, Stefano Taddei, Antonio Salvetti. Internal Medicine, University of Pisa, Pisa, Italy. A reduced endothelium(END)-dependent flow mediated dilation (FMD) has been demonstrated in the large arteries of essential hypertensive patients (EH). However no information is available on receptor operated END-dependent vasodilation (VD). Moreover it is still assessed whether in large arteries endothelial dysfunction is characterized by an impairment in nitric oxide (NO) availability. In this study we evaluated whether receptor-operated END-dependent VD is impaired in EH and the possible alteration of NO availability. RA FMD following forearm reactive hyperemia (RH) induced by 5 minutes of ischemia (pediatric cuff on the wrist), and response to intrabrachial infusion of ACh (1.5 and 15 ␮g/100 ml/min), in absence or presence of L-NMMA (100 ␮g/100 ml/min), a NO synthase inhibitor was measured in 6 EH (42⫾10 years, 152⫾8/99⫾7 mmHg) and 6 normotensive subjects (NS) (39⫾9 years, 123⫾9/82⫾6 mmHg). RA diameter was measured by an automatic edge detection system from end-diastolic scans from high resolution ultrasounds (Esaote AU5 Armonic) acquired every second on personal computer. Baseline diameter was the mean value of measurements obtained in one minute stimulus application. Blood flow velocity was measured by pulsed doppler to calculate RH after ischemia and RA blood flow changes after drug infusions. Vascular responses were calculated as the maximal percentage change above baseline. FMD was significantly (p⬍0.01) reduced in EH (4.4⫾1.2%) as compared to NS (6.0⫾0.9%). RH was similar in the two groups (EH: 509⫾154%; NS: 470⫾179%). EH also showed a reduced response to ACh-induced increase in RA diameter (2.4⫾0,7%; 6.5⫾2.4% vs NS: 6.4⫾0.7%; 12.9⫾3.1%; p⬍0.001) and flow (6⫾2%; 35⫾18% vs NS: 25⫾9%; 72⫾24%; p⬍0.01). In NS, L-NMMA reduced RA diameter (-4.9⫾0.6%), blunted FMD (3.5⫾0.7%; p⬍0.01 vs baseline), without modifying RH (460⫾343%) and reduced (p⬍0.01 vs baseline) AChinduced increase in RA diameter (2.7⫾1.9%; 5.7⫾3.7%) and flow (3⫾1%; 45⫾23%). In HT, L-NMMA, which caused similar reduction in RA diameter (-3.6⫾1.8%), did not change FMD (EH 5.0⫾1.6%), RH (788⫾160%) or ACh-induced increase in RA diameter (4.7⫾2.4%; 7.2⫾3.9%) and flow (2⫾1%; 38⫾21%). EH showed a reduced END-dependent response in the RA artery as compared to NS. This alteration seems to be due to a reduced NO availability. Key Words: Nitric Oxide, Flow Mediated Dilation, Essential Hypertension