Systemic and regional hemodynamic effects of subchronic high water intake

AIH-APRIL 1995-VOL.8, NO.4, PART 2

POSTERS: Other Therapeutic Agentsor Modalities :33A

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G9 EVIDENCE FORMfELIORATlON OFENDOTHELIAL CELL DYSFUNCfION RV ERYTHROPOIETIN THERAPY IN PRE-DIALYSIS HYPERTENSIVE PATIENTS

S. Kuriyama', Y, Utsunemiya, H. Yoshida, H.Tomonari', T. Hashimntn, Division ofNephroillgy, Saiseikai Central Huspital and Internal Medicine II, likel Univers!ly, Tukyo, Jcpan The invnlvementof endothelial cells inIhe pathngenesls of erythropoietin-induced hypertension has been postulated. Addilionall}', evidences for endothelial ~'CII damages have emerged inpatients with chronic renal failure (CRF). We thus investigated the effect of human recombinant erythropoIetin Ilit'rapy (rHuE/JO) on endothelial cell functions in pre-dialysis pallems wilh progressive anemia, Serum ihrombomodulln (Tm) and plasma endmhelin-I (ET-l) corcentratlon in pre.dialysis patients were higher than thaI In agc-, and sex-matched normal subjects(N) (Tm: 7.9 :l: 2.11 FU/ml (n=I11) for CIlF patients vs, 3,5 :t 0.7 FUlml(n::28)fur N(p
KeyWords: Erythropoietin, Enduthelial Cells, Bndoibelin,

SYSTEMIC AND REGIONAL HEMODYNAMIC EFFECTS OF SUBCHRONIC HIGH WATER INTAKE N MQore, R Joannldes, C Schocnrnekers-Smits, EI H Bakkall, V de la Gucrroniere", V Richard, C Thuillez Dept of Pharmacology, Vacomed, CHU de Rouen 76031 Rouen Codex, and *Evian, Paris Acute normovolcmic hemodilution has been shown to result in decreased vascular resistance and increllsed peripheral blood now, with increased tissue oxygen delivery, generally attributed to decreased blood viscosity. However, all trials to date have used invasive dilution. We therefore studied lhe hemodynamic effects of a two-week oral mineral water overload (Evian@. 3 liters per day) in 8 ~eallhy volunteers with nonnal renal function. The following parameters were evaluated using non-Invasive techniques: I) radial artery diameter, and wall thickness (NIUS-2 echotracklng angiometcr); 2} radial artery now (doppler): 3) digital blood pressure (Finapres®); 4) forearm capillary flow (laser Doppler Ilowmetry), 5) cardiac output (bioimpedance Bomed NCCOM3) and 6) blood chemistry. After 2 weeks of high water intake (3.2iO.l vs 1.7±O.1 Ilday basal intake), there VIas no significant change in heart rate, blood pressure, cardiac index, systemic resistance, or body weight. Radial anerial diameter increased from 2.86±O.07 to 3.06:1;0.07 mm (pc::O.OS), radial wall thickness decreased from 0.47iO,02 to 0.46±O.02 mm (p
Thrombnmudufln

Regional hemodynamics, Systemic hemodynamics, Subchronlc high water intake, vasodnauon.

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DIRECT GENE DELIVERY OF HUMAN TISSUE KALLIKREIN REDUCES BLOOD PRESSURE IN SPONTANEOUSLY HYPERTENSIVE RATS. Julie Chao and Lee Chao. Medical University of South Carolina, Charleston, SC 29425

INFLUENCE OF AUTOHEMOTHERAPY WITH OZONE ON BLOOD PRESSURE AND CARDIOVASCULAR RISK FACTORS IN PATIENTS WITH MILO HYPERTENSION. K KrAft·, E Stenkamp, and H Vetter. Hedical Policlinic, University of 1Ionn, Germany

Extensive studies indicate that the tissue kallikreinkininsystem is involved in bloodpressure homeostasis. We have recently developed transgenic micewhichoverexpress human tissue kallikrein under various promoter/enhancer control. These transgenic mice are hypotensive and their blood pressure can be reversed by injecting aprotinin (a kallikrein inhibitor) or Hoe l40 (a bradykinin receptor blocker). We further investigated theeffectof human tissue kallikrein gene delivery by intravenous, intramuscular and intraperitoneal injection of kallikrein gene constructs into spontaneously hypertensive rats (SHR). Expression of the human tissue kallikrein gene in SHR was identified by reverse transcription-Pf'R by Southern blot analysis and ELISA. Somatic gene delivery of human tissue kallikrein into SHR caused a reduction of systemic blood pressure one week post-injection and thiseffect continued for two months. The blood pressure reduction wasmore than 20 mmHg compared to controls which wereinjected withvector DNAalone. The differences are statistically significant indicating that direct delivery of the human tissue kallikrein genz induces a sustained reduction of systemic blood pressure in SHR. The hypotensive effect caused by somatic genedelivery of human tissue kallikrein in SHRis reversed by subcutaneous injection of aprotinin. Antibodies to eitherhuman tissue kallikrein or kallikrein DNA were not detected in rat sera following injection ciFthe human tissue kallikrein gene. These results raise the potential of applying kallikrein gene therapy for treating human hypertensive diseases,

Autohemotherapy with ozone! (A03} is frequently used by physiatricians to improve the general condition of elder patients with atherosclerosis, but never before has been evaluated in controled studies. In a randomized double-blind placebocQntr~lle1 cross-over study with a free interval of 15 w~eks, the effects ~f 10 A03 und 10 autohemotherapies with oxygen (A0 2) (2 applications/week) on bl¢od p,essure (24h ambulatory b).ood pressure measurement), aggregation of thrombocytes and lipid metabolism were evaluated in 17 ~:ierwise untreated patients with mild hypertenaion (25-64 years of age). Three patients had to be discontinued bec3use of thrombophlebitis or technical problems. After A03, mean 24h systolic and diastolic blood pressure was significantly lowered when comparea to pretreatment: l41~2 VB. 137t8 rom Hg (p
Key ~otds: . Somahc genedelivery, hypertension, human tissue kallikrein, hypertensive rats, aprotinin