beraprost and Hypertension

Prostacyclin (PGI2) inhibits platelet aggregation and vasoconstriction. PGI2 synthase (PTGIS), a catalyst of PGI2 synthesis from prostaglandin H2, is widely distributed and predominantly found in vascular endothelial and smooth muscle cells. The PTGIS gene is localized to 20q13.11-13 and a candidate gene for cardiovascular disease. We discovered mutations and polymorphisms in this gene and reported that they were associated with essential hypertension, myocardial infarction, and cerebral infarction. These results suggest that PGI2 function depends on the different alleles of the PTGIS gene and that they may influence the risk of cardiovascular disease. Thus, individualized management strategies, such as the administration of PGI2 analogues, could be selected for variants of this gene, to help prevent the development of cardiovascular disease.

Topics: Adult; Aged; Animals; Base Sequence; Cardiovascular Diseases; Cerebral Infarction; Cytochrome P-450 Enzyme System; Epoprostenol; Female; Genetic Predisposition to Disease; Humans; Hypertension; Male; Middle Aged; Molecular Sequence Data; Mutation; Myocardial Infarction; Patient Selection; Pedigree; Phenotype; Platelet Aggregation Inhibitors; Polymorphism, Genetic; Precision Medicine; Risk Factors; Treatment Outcome; Vasodilator Agents

Beraprost sodium (BPS, an analogue of prostacyclin) and telmisartan (TS, an angiotensin receptor blocker) have been reported to have a preventive effect on arterial stiffness in patients with cardiovascular diseases. The purpose of this study was to estimate the effects of a combined therapy using BPS and TS on arterial pulse wave velocity (PWV) values in elderly patients with hypertension and cerebral infarction. Over a 3-month period, 80 subjects with hypertension and histories of cerebral infarction received BPS only (120 microg/day p.o.), TS only (40 mg/day p.o.), both BPS and TS, or no medication at all (control). Arterial PWV and ankle brachial indices (ABI) were determined prior to and after 3 months of drug administration. During the follow-up, there were no significant changes in any of the parameters monitored with the exception of a significant decrease in systolic blood pressure in the BPS only, TS only, and BPS plus TS groups when compared to controls. The difference values for PWV in the control group, BPS only group, TS only group, and BPS plus TS group were +232.5, -114.6, -151.5, and -248.1 cm/s, respectively. The reduction values were significantly more pronounced in the BPS plus TS group than in the BPS only (P=0.037) and the TS only (P=0.022) groups. When BPS is combined with TS, an overall additive effect is seen in the improvement of PWV in Japanese patients with hypertension and cerebral infarction. This combination therapy is more beneficial than the corresponding monotherapies.

Topics: Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Arteriosclerosis; Benzimidazoles; Benzoates; Blood Flow Velocity; Cerebral Infarction; Double-Blind Method; Drug Therapy, Combination; Epoprostenol; Female; Humans; Hypertension; Male; Platelet Aggregation Inhibitors; Telmisartan; Treatment Outcome

Persistent pulmonary hypertension of the newborn (PPHN) is one of the most serious conditions in neonates resulting in a high mortality and morbidity. New alternative therapies for PPHN have been sought to improve survival and reduce morbidity.. To report an initial experience of using beraprost sodium (BPS) to treat infants with PPHN and to assess its effect on oxygenation and hemodynamic stability over a 72-hour study period.. The clinical data of neonates who received BPS as an adjunctive therapy for PPHN in our hospital between July 2007 and June 2008 were retrospectively reviewed.. During the study period, 7 infants with PPHN were successfully treated with BPS. The mean gestational age and birth weight were 39.3 ± 1.5 weeks and 3,365.7 ± 569.8 g, respectively. BPS was initiated at a median age of 42.7 h after birth (range: 2.1-166.5 h) with a baseline mean oxygen index (OI) of 33.9 ± 15.7 and a baseline mean systolic blood pressure (SBP) of 79.4 ± 9.9 mm Hg. The mean difference of OI at 24, 48 and 72 h following the treatment was -15.7 ± 14.8 (p = 0.043), -18.2 ± 12.3 (p = 0.018) and -16.7 ± 17.5 (p = 0.042), respectively. The mean SBP was significantly reduced as early as 6 h after initiation of treatment (-11.1 ± 11.5 mm Hg, p = 0.034) without changes in heart rate. Three cases were complicated with chronic lung disease, and the remaining 4 cases were normal at hospital discharge. No neurodevelopmental and cardiopulmonary disorders were observed in all cases at 1 year of age.. BPS may be used as an alternative treatment for infants with PPHN giving a significant improvement in oxygenation.

Topics: Blood Pressure; Epoprostenol; Female; Gestational Age; Humans; Hypertension; Infant, Newborn; Male; Persistent Fetal Circulation Syndrome; Retrospective Studies; Treatment Outcome; Vasodilator Agents

To clarify the function of polymorphonuclear leukocytes (PMN) in spontaneously hypertensive rats (SHR) and the effect of beraprost sodium (BS) on these functions, we examined superoxide anion (O2-) production and adherent activity by PMN, as well as modification of these functions by BS ex vivo and in vitro. In study 1, we measured PMN functions in 4-week-old SHR and Wistar-Kyoto (WKY) rats. In study 2 (ex vivo), 14-week-old SHR received vehicle (n = 6) and BS (30 microg/kg/day [n = 6] and 100 microg/kg/day [n = 7]) once daily for 4 weeks. In study 3 (in vitro), PMN from 18-week-old SHR were incubated with BS (0.1 and 1 micromol/L) and theophylline (200 micromol/L), which is reported to inhibit the PMN O2- production. Systolic blood pressure, platelet counts, and PMN O2- production stimulated by phorbol ester myristate acetate were significantly elevated in 4-week-old SHR compared with WKY (P < .05). Beraprost sodium decreased the ex vivo PMN O2- production, serum superoxide dismutase activity, and platelet counts (P < .05); however, BS did not reduce the in vitro PMN O2- production. These data support our hypothesis that the enhanced PMN function contributes to the cardiovascular damages during the early phase of SHR, and that BS has merit for preventing the O2- related organ damages in this model.

Topics: Animals; Anti-Inflammatory Agents; Blood Pressure; Body Weight; Epoprostenol; Hypertension; Male; Neutrophils; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Superoxides

A 60-year-old man with dermatomyositis was admitted to our hospital because of dyspnea and hypertension. He had high fever and convulsive seizures after admission. Laboratory examinations showed hemolytic anemia, thrombocytopenia, and renal failure. A clinical diagnosis of thrombotic thrombocytopenic purpura (TTP) was made. He failed to respond to plasma exchange therapy, pulse therapy with methylprednisolone, high-dose gamma-globulin therapy, and antiplatelet therapies with ticlopidine, dipyridamole and a prostacyclin analog of beraprost sodium. He died on his 17th day in hospital. Autopsy examination revealed widespread microthrombi in his kidneys, lungs, spleen, and intestine. Only seven cases of dermatomyositis or polymyositis complicated by TTP have been cited in the literature. TTP was fatal in 6 of these 7 cases. Early diagnosis and prompt treatment may improve the outcome of TTP patients with dermatomyositis. Dermatologists should keep in mind that TTP occasionally arises as a serious complication of dermatomyositis.

Topics: Anti-Inflammatory Agents; Dermatomyositis; Dipyridamole; Dyspnea; Epoprostenol; Fatal Outcome; Fever; gamma-Globulins; Humans; Hypertension; Immunization, Passive; Male; Methylprednisolone; Middle Aged; Plasma Exchange; Platelet Aggregation Inhibitors; Purpura, Thrombotic Thrombocytopenic; Seizures; Ticlopidine; Treatment Outcome

Beraprost sodium is a stable analog of the vasodilator, platelet antiaggregatory eicosanoid, prostacyclin. Experiments were performed to determine whether long-term therapy with beraprost produces vascular protective effects in saline-drinking stroke-prone spontaneously hypertensive rats (SHRSPs). Oral beraprost at 30, 100, or 300 micrograms/kg/day starting at 8.4 weeks of age did not affect the progressive increase of systolic blood pressure (measured by tail-cuff plethysmography) in these rats. Additional experiments in SHRSPs, prepared for continuous monitoring of blood pressure by radiotelemetry, revealed that oral beraprost administration reduced mean arterial pressure but that these hypotensive responses were not sustained (< 4 h). In all SHRSPs receiving oral beraprost, proteinuria and cerebrovascular lesions developed. In contrast, continuous subcutaneous infusion of beraprost at 2.8 mg/kg/day from age 8.3-12.3 weeks reduced systolic blood pressure and markedly diminished the development of renal lesions and the occurrence of stroke in saline-drinking SHRSPs. Beraprost at 0.9 mg/kg/day reduced blood pressure less than did 2.8 mg/kg/day and provided partial protection against cerebral and renal lesions after a 4-week infusion period. These results indicate that long-term subcutaneous infusion of beraprost can protect saline-drinking SHRSPs against stroke and renal damage. This effect is not readily dissociated from the ability of beraprost to reduce blood pressure in SHRSPs.

Topics: Administration, Oral; Animals; Blood Pressure; Cerebrovascular Disorders; Drug Evaluation, Preclinical; Epoprostenol; Heart; Heart Rate; Hypertension; Injections, Subcutaneous; Kidney; Male; Organ Size; Rats; Rats, Inbred SHR; Vasodilator Agents