Urinary 6-keto-PGF1 alpha after captopril and indomethacin: possible contribution of PGI2 to the antihypertensive mechanism of ACE inhibitors.
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6-Ketoprostaglandin F1 alpha↗
Biomedical subjects
P Minuz
Publications and source records attributed to P Minuz.
Increased sodium-lithium countertransport in red cells of patients with Bartter's syndrome.
Erythrocyte sodium-lithium countertransport was evaluated in three adult patients with Bartter's syndrome, diagnosed on clinical and histopathological basis and on laboratory tests. As compared with age-matched control subjects, lithium effluxes to both sodium medium and to sodium-free medium were high in two patients and Na+-Li+ countertransport was significantly greater in all three patients. The relationship between increased Na+-Li+ countertransport and the proposed primary disorder of Bartter's syndrome (i.e., a primary tubular defect of chloride reabsorption) is not apparent. However, this finding favours the hypothesis of a generalized cellular membrane dysfunction of ion transport in Bartter's syndrome.
Adult↗
Carbenoxolone and prostaglandin E2 and F2 alpha gastric juice levels in man.
The purpose of the present study is to evaluate the effect of carbenoxolone after a non-oral administration on the levels of prostaglandins E2 and F2 alpha in gastric juice. The gastric secretion of 6 healthy volunteers (in basal conditions and after administration of a stimulus of 6 micrograms/kg weight of pentagastrin i.m.) was studied before and after seven days of treatment with 150 mg b.i.d. of carbenoxolone suppository. Concentration and output of prostaglandins E2 and F2 alpha (measured by radioimmunoassay), hydrochloric acid, pepsin and N-acetylneuraminic acid in gastric juice were determined. Compared to control values, no statistically significant difference in acid, pepsin or prostaglandin F2 alpha content, or in gastric juice volume, was observed after treatment. However a significant increase was observed in the concentration and output of prostaglandin E2 after administration of pentagastrin. The concentration and output of N-acetyl-neuraminic acid increased significantly only in basal conditions in carbenoxolone-treated subjects. The present study suggests that the cytoprotective action of carbenoxolone on gastric mucosa in man could be due to an increased prostaglandin E2 activity. This effect is observed after rectal administration, therefore suggesting that carbenoxolone also has a systemic action.
Carbenoxolone↗
Reduction of the antihypertensive effect of captopril induced by prostaglandin synthetase inhibition.
The effects of prostaglandin synthetase inhibition by indomethacin on blood pressure and hormonal variations induced by captopril were studied in eight patients with essential hypertension and in six nonhypertensive subjects. Captopril antihypertensive effect and captopril-induced plasma renin increase were almost totally abolished by a short-term administration of indomethacin (50 mg t.i.d.). These results support the hypothesis that prostaglandins contribute to the antihypertensive effects of ACE inhibitors. It may be of clinical importance that anti-inflammatory drugs that inhibit PG-synthetase can also blunt the antihypertensive action of ACE inhibitors.
Adult↗
[The effect of dopaminergic stimulation and inhibition on the urinary excretion of aldosterone and kallikrein in spontaneously hypertensive rats].
The effect on the electrolyte balance of a dopaminergic agonist (bromocriptine) and an antagonist (metoclopramide) and their effect on renal aldosterone and kallikrein excretion were investigated. Ten normotensive Wistar rats and ten spontaneously hypertensive rats (SHR-Wistar Kioto) were treated with BCR (4 mg/Kg weight b.i.d.) for 4 days; after a week of pharmacological wash-out they received MCP (0,5 mg/Kg weight b.i.d.) for 4 days. Before and after treatment and at the 2nd and 4th day of each treatment diuresis, urinary excretion of aldosterone, kallikrein, sodium, potassium and proteins were measured. During the 24-hour urine collections the rats were kept in separate metabolic cages with free access to food and water. Kallikrein urinary excretion was lower in SHR than in normotensive rats under basal conditions (p 0.05); urinary sodium, potassium, proteins and sodium/potassium rate were also reduced in SHR. After treatment with bromocriptine a further reduction in urinary kallikrein excretion was observed in SHR. After MCP all the parameters were unchanged both in normotensive rats and in SHR, but SHR showed a significant correlation between aldosterone and kallikrein excretion (p less than 0,001); in this condition it seems that in SHR the control exerted by aldosterone on kallikrein excretion is greater than the one exerted by dopamine. It may indicate a defect of the natriuretic and vasodilator dopaminergic system in spontaneously hypertensive rats.
Aldosterone↗
A discrepancy between the effects of a single oral dose of captopril on blood pressure, plasma renin activity, and serum angiotensin-converting enzyme levels.
The effects of a single oral dose (100 mg) of the angiotensin-converting enzyme (ACE) inhibitor, captopril (SQ 14,224), on blood pressure (BP), plasma renin activity (PRA), plasma aldosterone (PA), and serum ACE were investigated in 18 patients with essential hypertension (EH) and in 4 with renovascular hypertension (RVH). in most patients, SQ 14,225 caused a significant reduction of BP during the subsequent 6 h, particularly in RVH patients. A significant correlation between basal PRA levels and BP reduction was observed only by considering all the patients together. After ACE blockade, a significant increase of PRA was observed in RVH and in normal-renin EH patients, but not in EH patients with lower PRA. Maximal serum ACE inhibition (over 50%) occurred after 2 h but diminished after 4 h and 6 h, whereas the BP decrease persisted for 6 h. After 3-day treatment with indomethacin (six patients) captopril's antihypertensive action was blunted, despite a reduction of baseline PRA levels and of captopril-induced PRA elevation. The antihypertensive effects of SQ 14,225 in low-renin EH patients, the lack of effect of ACE blockade on renin secretion in these patients, and the reduction of the antihypertensive effects of SQ 14,225 after indomethacin refute the interpretation of purely angiotensin-related antihypertensive mechanism.
Administration, Oral↗
[Significance of some changes induced in the vasoactive systems of renin and kallikrein during diuretic treatment of arterial hypertension].
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Adult↗
Kidney 15-hydroxy-prostaglandin-dehydrogenase activity during the development of experimental hypertension in the rat.
15-hydroxy-prostaglandin-dehydrogenase (PGDH) activity was studied in rat kidney homogenates during the development of hypertension, within 20 days after left renal artery constriction by a solid silver clip. In the ischemic kidney PGDH activity increased at day 6, reached maximum at day 10, then progressively at day 15 and returned to normal levels at day 20. No difference was found between contralateral kidneys and kidneys of normotensive control rats. Variations of PGDH activity did not seem to be related to either renal perfusion pressure or renin production. Increased PGDH activity may be a consequence of an enzyme induction following increased PG-synthetase activity, or it could be viewed as a defence mechanism, according to the hypothesis of a prohypertensive effect of PG in the rat.
Animals↗
Vasodilating properties of a new non-steroidal anti-inflammatory drug, nitroflurbiprofen, on rat aortic rings.
The effects of nitroflurbiprofen (NFP), a new non-steroidal anti-inflammatory drug containing a nitroxybutyl moiety, on rat aortic rings were compared with those of flurbiprofen (FP) and glyceryl trinitrate (GTN). NFP and GTN relaxed, in a dose-dependent manner, either intact or rubbed aortic rings precontracted with epinephrine. Pretreatment with FP did not influence the relaxant activity of NFP in both endothelium-intact and -denuded arteries. In unrubbed preparations, FP did not affect contraction induced by epinephrine, while in rubbed ones a moderate relaxation was observed. Methylene blue and oxyhaemoglobin completely reversed the vasodilating effect of NFP in both rubbed and unrubbed preparations. Moreover, the addition of cysteine 5 mmol l-1 at the end of the cumulative application of NFP resulted in a further relaxation of aortic rings. These results indicate that NFP possesses vasodilatory activity which appears to be dependent on the release of nitric oxide or nitric oxide derivatives.
Animals↗
[Endothelial function and the microcirculation in diabetes mellitus].
The role of endothelial dysfunction in the pathogenesis of diabetic microangiopathy is reviewed. Reversible alterations in microcirculation, consisting of increased capillary pressure, blood flow and endothelial permeability, can be detected at an early stage in diabetes mellitus. Irreversible structural modifications of the vascular wall, such as thickening of the basal membrane due to the extracellular accumulation of proteins, take place at later stages. Atherosclerosis further affects microcirculation in diabetes mellitus by decreasing autoregulatory capacity and blood flow reserve. Endothelial dysfunction has been observed to precede the onset of microvascular lesions, as demonstrated by reduction in the vasodilatory response to vasoactive agents and by alterations in the antithrombotic properties of the endothelium. Experimental data available so far suggest that endothelial dysfunction may be directly related to hyperglycemia. Abnormalities in lipoprotein metabolism, generation of glycation end products, and increased oxidative stress may also be responsible for the endothelial dysfunction in diabetes mellitus. Insulin resistance appears to be related to endothelial dysfunction in non-insulin-dependent diabetes mellitus through a reduction in the biological activity of endothelial-derived nitric oxide.
Animals↗
NCX4016 (NO-aspirin) inhibits thromboxane biosynthesis and tissue factor expression and activity in human monocytes.
BACKGROUND: NCX4016 (2 acetoxy-benzoate 2-(2-nitroxymethyl)-phenyl ester, NicOx S.A., France) is an antithrombotic agent chemically related to acetylsalicylic acid (ASA). We hypothesised that NCX4016, being able to release nitric oxide (NO) and to inhibit cyclo-oxygenase, might inhibit the prothrombotic function in human monocytes. MATERIAL AND METHODS: The effects of NCX4016 and ASA on the release of thromboxane (TX) B2 and tissue factor expression and activity were compared using adherent human monocytes. The tested drugs were added before stimulation with 10 Kg/ml LPS and incubation lasted 6 hours. TXB2 concentration was measured by RIA in the supernatant of cultured cells. Immunoreactive tissue factor (TF) concentration was determined by enzyme-linked immunoassay and TF activity was assayed by measuring the peptidyl activity of the tissue factor/ factor VII complex. RESULTS: Both ASA and NCX4016 10-300 Kmol/L dose-dependently reduced TXB2 release. NCX4016 activity was comparable to that of equimolar ASA. Part of the activity of NCX4016 up to 100 Kmol/L was prevented by 10 Kml/L ODQ, inhibitor of cGMP generation. Immunoreactive TF was dose-dependently inhibited by 300 Kmol/L NCX4016, but not by ASA. Also tissue TF activity was reduced by 300 Kmol/L NCX4016, but not by ASA. CONCLUSIONS: The present results indicate that NCX4016 not only has anti-platelet effects but also inhibits prothrombotic activities in human monocytes, partly via NO-dependent mechanisms. NCX4016 may prove effective in the clinical setting of athero-thrombosis.
Aspirin↗
[Correlations between urinary prostaglandins, placental hormones and prolactin in the first pregnancy trimester].
In the first weeks of pregnancy there is a significant increase of vasodilatator prostaglandins in maternal blood. This increase could be in a cause-effect relation with the increase of progesterone, BHCG and HPRL typical of the first phase of pregnancy. Blood samples of 12 normotensive women reveal that there is not a correlation between placental hormons, HPRL and the increase of prostaglandins, but these hormones seem to offer an important control on other more complex biochemical mechanisms that cause the increase of vasodilator prostaglandins.
Blood Pressure↗