15-keto-13-14-dihydroprostaglandin-f2alpha and Hypertension

The present study was designed to analyse whether hypertension alters the involvement of cyclooxygenase-2-derived mediators in phenylephrine-induced vasoconstrictor responses.. Vascular reactivity experiments were performed in aortic segments from normotensive, Wistar-Kyoto, and spontaneously hypertensive rats (SHR); protein expression was measured by western blot and/or immunohistochemistry, and prostaglandin F2alpha (PGF2alpha), 8-isoprostane and prostacyclin release were determined by enzyme immunoassay commercial kits.. The protein synthesis inhibitor dexamethasone (1 micromol/l), the non-selective cyclooxygenase inhibitor indomethacin (10 micromol/l), the selective cyclooxygenase-2 inhibitor NS 398 (1 micromol/l), and the thromboxane A2/prostaglandin H2 (TP) receptor antagonist SQ 29,548 (1 micromol/l), reduced the concentration-response curves to phenylephrine more in segments from hypertensive than from normotensive rats; however, the thromboxane A2 (TxA2) synthase inhibitors furegrelate (10 micromol/l) and OKY 046 (1 and 10 micromol/l) had no effect in either strain. Removing endothelium or adding dexamethasone almost abolished the NS 398 effect. Cyclooxygenase-2 protein expression, which was reduced by dexamethasone, was higher in aorta from hypertensive animals. In both strains cyclooxygenase-2 was localized mainly in endothelial cells and adventitial fibroblasts. 13,14-Dihydro-15-keto-PGF2alpha, 6-keto-PGF1alpha and 8-isoprostane levels were greater in the medium from hypertensive than from normotensive rats; NS 398 decreased levels of the three metabolites studied only in the medium from SHR.. PGF2alpha and 8-isoprostane seem to be involved in the response to phenylephrine in rat aorta; this involvement is greater in hypertensive rats, probably due to a higher endothelial induction of cyclooxygenase-2.

Topics: Animals; Aorta; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprost; Endothelium, Vascular; Hypertension; Male; Nitrobenzenes; Phenylephrine; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sulfonamides; Vasoconstriction; Vasoconstrictor Agents

The concentrations of 13,14-dihydro-15-oxo-prostaglandin F2 alpha (PGFM), 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) and thromboxane B2 (T X B2) were measured by radioimmunoassay in peripheral plasma from 183 pregnancy women attending routine antenatal clinics. A total of 141 patients (47 nulliparous, 94 parous) remained normotensive and had uncomplicated pregnancies. The results from this group showed that there was no significant difference in the concentration of any metabolite in relation to parity or gestational age. The concentrations (pmol/l; means +/- SD) were PGFM 373 +/- 105, 6-oxo-PGF1 alpha 391 +/- 104 and T X B2 373 +/- 121. Nineteen patients (12 nulliparous, 7 parous) who had pregnancy-induced hypertension (PIH) by the time of sampling (three) or who subsequently developed the symptom (mean time from sampling to diagnosis 11 weeks, range 1-24 weeks) had significantly higher levels of 6-oxo-PGF1 alpha (574 +/- 216; P less than 0.0005, Student's t-test) and T X B2 (603 +/- 268; P less than 0.0005). The concentrations in seven nulliparous patients with PIH and proteinuria were 656 +/- 276 for 6-oxo-PGF1 alpha and 754 +/- 228 pmol/l for T X B2.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Dinoprost; Female; Humans; Hypertension; Parity; Pregnancy; Pregnancy Complications, Cardiovascular; Prostaglandins F; Radioimmunoassay; Thromboxane B2; Thromboxanes

A dynamic study is made of the content of PGE and PGF2 alpha in the kidneys of rats with experimental coarctation hypertension, as well as the PGF2 alpha-metabolite in the blood plasma of the same experimental model in rats and in patients with arterial hypertension. The level of the PGF2 alpha-metabolite tends to decrease both in the animals with experimental hypertension and in hypertonic patients. In rats with 30-day hypertension low values are established in 55 per cent, while in 45 per cent there are high values of the PGE level in the kidney homogenate compared with the control group. The concentration of PGF2 alpha in the left ("endocrine") kidney (whose artery originates distally from the place of aortic coarctation) is higher than the concentration of the same PG in the right kidney. Our findings give grounds for the following assumptions: 1. The PGF2 alpha-metabolite as hormone and partly PGE in the kidneys seem to be involved in the pathogenesis of arterial hypertension as compensatory factors. 2. PGF2 alpha in the kidneys probably participates directly as one of the elements of the complex pathogenesis of arterial hypertension.

Topics: Adolescent; Adult; Animals; Biotransformation; Dinoprost; Female; Humans; Hypertension; Kidney; Male; Middle Aged; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains