DOCA-salt hypertensive rats. Carotid arteries of DOCA and sham rats were transduced ex vivo with GTPCH I or -galactosidase genes via adenoviral vectors, and recombinant GTPCH I was quantified 24 hrs later. GTPCH I activities and BH4 levels were determined by HPLC. Arterial O 2 - was assayed by dihydroethidium confocal microscopy and lucigenin chemiluminescence. Vascular function was measured by iso- metric tension recording. ET-1 treatment of normal arteries (10 nM, 4 hrs) significantly increased O 2 - and reduced BH4 levels (4.00.6 vs. 5.90.9 pmol/mg protein, n=5, p0.01), which were abolished by ET A antagonist ABT-627 or NADPH oxidase inhibitor apocynin. There were significantly elevated arterial O 2 - and decreased BH4 levels (3.20.4 vs.5.70.6 pmol/mg protein) and GTPCH I activities (4.60.5 vs. 6.00.7 pmol/hr/mg protein, both n=5, p0.05) in DOCA compared to sham rats. Treatment of arteries of DOCA rats with ABT-627 or apoc- ynin abrogated O 2 - and restored BH4 levels. Both endothelium-depen- dent NO-mediated relaxation to acetylcholine and basal NO release (66.35.9 vs. 24.31.4 pmol/hr/mg protein, n=6, p0.01) were re- duced in arteries of DOCA rats. Recombinant GTPCH I protein was detected in arteries 24 hours after gene transfer, resulting in restoration of GTPCH I activities (4.00.5 vs. 8.30.98 pmol/hr/mg protein) and BH4 levels (3.20.4 vs.7.60.5 pmol/mg protein, both n=5, p0.01) in DOCA rats. Furthermore, gene transfer of GTPCH I significantly reduced arterial O 2 - levels, with a concomitant restoration of endothelium- dependent relaxation and basal NO release (24.31.4 vs. 76.64.98 pmol/hr/mg protein, n=6, p0.01) in DOCA rats. Conclusions: Arterial BH4 was reduced by ET-1-induced O 2 - via an ET A /NADPH oxidase pathway, resulting in endothelial dysfunction, which was restored by GTPCH I gene transfer in DOCA-salt hyperten- sion. Key Words: Tetrahydrobiopterin, GTP Cyclohydrolase I, Superoxide P-98 MICROALBUMINURIA AND ENDOTHELIAL ACTIVATION IN TREATED AND UNTREATED DIABETIC AND NON-DIABETIC HYPERTENSIVES Santina Cottone, Giuseppe Mule `, Emilio Nardi, Rosalia Arsena, Chiara Briolotta, Maria Carmela Lorito, Anna Vadala `, Giovanni Cerasola. Dipartimento di Medicina Interna, Malattie Cardiovascolari e Nefrourologiche, Policlinico P.Giaccone, Univerisity, Palermo, Italy. Many interventional trials demonstrated a greater efficacy of certain classes of drugs in treating target organ damage in essential hypertension and diabetic nephropathy. In order to evaluate if blood pressure control alone, inedependently of pharmacologic classes, influences endothelial activation positively, we studied 234 consecutive hypertensive outpatients coming to our clinic for the first time. All subjects underwent OGTT, renal function analysis,oral glucose tolerance test (OGTT), soluble forms of plasma ICAM-1, VCAM-1 and E-Selectin(E-Sel), plasma von Willabrand factor (vWf), and the assay of 24h microalbuminuria (MAU). We further studied 40 healthy normotensives.Out of the 234 subjects, 80 were untreated- and 92 were treated- (2–3 drugs) essential hypertensives (EH), whereas 62 were on antihypertensive therapy and resulted diabetics after OGTT. E-Selec- tin correlated significantly (p0.001) with MAU in all groups of patients. Diabetic disease seems to induce a further endothelial acitvation when associated with hypertension. Antihypertensive therapy, when not selected to prevent organ damage, does not seem to influence endothelial activation in non-diabetic EH. Nonetheles, it is to consider a probably longer duration of hypertensive disease in treated patients than in untreated. Key Words: Endothelial Activation, Microalbuminuria, Adhesion Mol- ecules P-99 ENDOTHELIAL DYSFUCNTION AND VASCULAR INFLAMMATION IN ESSENTIAL HYPERTENSION Maria Larroussse, Ernesto Bragulat, Marta Segarra, Cristina Sierra, Antonio Coca, Alejandro De la Sierra. Hypertension Unit. Department of Internal Medicine, Hospital Clinic, Barcelona, Spain. Essential hypertension in associated with endothelial dysfunction, which is the first step in the process of atherosclerosis. The aim of the study was to correlate the degree of endothelial dysfunction with levels of several serum markers implicated in the atherosclerosis development. Thirty- nine young non-treated essential hypertensive patients (26 males and 13 females) with a mean age of 40 years (range: 26-58) and without clinical evidence of organ damage were studied. Serum or plasma concentrations of the intracellular adhesion molecule type 1 (ICAM-1), vascular adhe- sion molecule type 1 (VCAM-1), P-selectine, E-selectine and monocyte chemoatractant protein-1 (MCP-1), as well as matrix metalloproteinases types 1, 2 and 9 (MMP-1, MMP-2 and MMP-9) and tissue inhibitor of metalloproteinases type 1 (TIMP-1) were determined by ELISA meth- ods. Endothelial function was assessed by determining the maximal acetylcholine-induced forearm vasodilation, as well as by measuring plasma and urinary levels of nitrites and nitrates (NOx), cyclic GMP and plasma endothelin. The degree of endothelial dysfunction correlated with several inflam- matory markers. In fact, the P-selectin concentration was inversely cor- related with maximal acetylcholine-induced forearm vasodilation (r=-0.536; p=0.002). Moreover, both P-selectin (r=-0.413; p=0.029) and MCP-1 (r=-0.376; p=0.037)were inversely correlated with plasma cyclic GMP, both E-selectin (r=-0.340; p=0.039) and MCP-1 (r=-0.462; p=0.004) inversely correlated with plasma NOx, and VCAM-1 directly correlated with plasma endothelin (r=0.350; p=0.036). Finally, plasma concentrations of TIMP-1 were inversely correlated with maximal acetylcholine-induced vasodilation (r=-0.404; p=0.024)and cyclic GMP (r=-0.427; p=0.023) and directly correlated with plasma endothelin (r=0.384; p=0.019). All these correlations were maintained after adjustment for mean blood pressure. In conclusion, in essential hypertension, there is a correlation between the degree of endothelial dysfunction and some serum atherosclerosis markers, espe- cially selectins and the tissue inhibitor of metalloproteinases type-1. Key Words: Endothelium-Dependent Vasodilation, Selectines and Ad- hesion Molecules, Matrix Metalloproteinases P-100 REGULATION OF SYSTOLIC BLOOD PRESSURE BY SEROTONIN, THROUGH 5-HT2B RECEPTOR, AND OVARIAN HORMONES IN NOS INHIBITION- INDUCED HYPERTENSIVE MICE Nelly Etienne, Lahcen Elfertak, Alain Guimont, Laurent Monassier, Luc Maroteaux. Institut de Genetique et de Biologie Moleculaire et Cellulaire, Illkirch, France; Institut Clinique de la Souris, Illkirch, France. 5-HT2B receptor male mutant mice exhibit a dilated cardiomyopathy, whereas female mutant mice with less severe histopathological findings did not reveal significant functional changes under steady-state condi- tions. In this study, we investigated whether cardiovascular functions of Results Untreated EH Treated EH Diabetic Hs cSBP mmHg 151 + 12 142 + 17 149 + 15 cDBP mmHg 94 + 4 86 + 5 86 + 10 ICAM-1 ng/ml 321 + 69 310 + 72 379 + 40** VCAM-1 ng/ml 1030 + 192 985 + 91 1189 + 181** E-Sel. ng/ml 82 + 12 84 + 9 96 + 11* vWf % 109 + 23 114 + 21 131 + 11** MAU mcg/min 18 + 23 22.5 + 31 49 + 31* *p  0.01, ** p  0.001 treated vs Diabetic hypertyensives 68A AJH–May 2004 –VOL. 17, NO. 5, PART 2 POSTERS: Endothelial Factors (endothelin, nitric oxide, etc.) Downloaded from https://academic.oup.com/ajh/article/17/S1/68A/174666 by guest on 21 March 2023