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Biomedical subjects

P Mehta

Publications and source records attributed to P Mehta.

At least 217 records · Page 12Linked to original sources
PubMed1983

Stimulation of vessel wall prostacyclin by selective thromboxane synthetase inhibitor OKY 1581.

Human umbilical veins have been shown to produce small amounts of TXA2 in addition to PGI2. We measured relative TXA2 and PGI2 production by umbilical veins in the presence of selective TXA2 synthetase inhibitor OKY 1581. OKY 1581 treatment resulted in inhibition of TXA2 but a marked increase in PGI2 release, which may relate to diversion of cyclic endoperoxides to PGI2 pathway or to removal of a feedback control at the level of AA mobilization.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Increased plasma concentrations of prostacyclin metabolite 6-keto-PGF1 alpha in essential hypertension. Influence of therapy with labetalol.

To evaluate the role of the vasoactive prostaglandins prostacyclin and thromboxane A2 in essential hypertension, the stable metabolites 6-keto-PGF1 alpha and thromboxane B2, respectively, were measured in plasma before and after therapy in 7 patients. During the placebo phase, plasma 6-keto-PGF1 alpha levels were significantly greater than normal. Plasma thromboxane B2 levels were not statistically different from those in normal subjects. After intravenous administration of labetalol to the point of blood pressure reduction, neither plasma 6-keto-PGF1 alpha nor thromboxane B2 values changed. With prolonged oral labetalol therapy and concurrent regulation of blood pressure, a significant decrease in plasma 6-keto-PGF1 alpha levels occurred while thromboxane B2 values remained unaltered. Elevation of plasma 6-keto-PGF1 alpha in untreated hypertensive subjects suggests that enhanced vessel wall prostacyclin synthesis may be a protective mechanism to prevent organ damage. As blood pressure is controlled this increase is no longer needed, and prostacyclin generation returns to normal.

Administration, Oral↗
PubMed1983

Comparative effects of nitroglycerin and nitroprusside on prostacyclin generation in adult human vessel wall.

The precise mechanism of vasodilatory actions of nitroso-compounds is not clear. It has been suggested that these drugs might modulate release of the vasodilator, prostacyclin, from cultured endothelial cells and bovine arteries or potentiate actions of prostacyclin. This study was designed to examine the effects of nitroglycerin and nitroprusside on prostacyclin release from adult human vasculature. Saphenous vein ring preparations were incubated with nitroglycerin or nitroprusside and arachidonic acid, the substrate for prostacyclin. Vascular rings incubated with nitroglycerin released significantly more prostacyclin (measured as 6-keto-prostaglandin F1 alpha, a stable hydrolysis product of prostacyclin by radioimmunoassay) compared with the control vascular rings (p less than 0.02). This increase was observed at the therapeutic concentrations of nitroglycerin (5 to 10 ng/ml). However, incubation of saphenous vein rings with nitroprusside in concentrations as high as 1 microgram/ml was not associated with any increase in prostacyclin release. Prior incubation of vascular rings with the cyclooxygenase blocker, indomethacin, inhibited nitroglycerin-induced prostacyclin release. Incubation of vascular rings with the selective thromboxane A2 blocker, OKY 1581, resulted in additional prostacyclin release with nitroglycerin treatment, presumably by inhibiting vessel wall-generated thromboxane A2. Nitroprusside had no significant effect on prostacyclin release from indomethacin-treated or OKY 1581-treated vascular rings. This study suggests significant stimulatory effects of nitroglycerin, but not of nitroprusside, on prostacyclin release from human saphenous vein. Nitroglycerin-induced prostacyclin release may be an important mechanism of its antiischemic actions in human subjects.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Influence of propranolol and 4-hydroxypropranolol on platelet aggregation and thromboxane A2 generation.

We examined in vitro effects of propranolol and its major metabolite, 4-hydroxypropranolol, on human platelets. Both propranolol and its 4-hydroxy metabolite had no significant direct effect on either platelet aggregation or TXA2 generation in therapeutic concentrations. Higher concentrations (greater than or equal to 10 micrograms/ml), however, reduced both parameters of platelet function. When propranolol and 4-hydroxypropranolol were incubated in combination with platelets in equal concentrations, there were synergistic effects on platelet aggregation and TXA2 generation. Neither propranolol nor 4-hydroxypropranolol inhibited platelet aggregation or TXA2 synthesis in sonicated platelets at any concentration, indicating that intact platelet membrane is necessary for their action.

Adenosine Diphosphate↗
PubMed1983

Effects of nitroglycerin on human vascular prostacyclin and thromboxane A2 generation.

We examined the effects of NTG on human saphenous and umbilical vein PGI2 and TXA2 generation. Vascular rings from both types of vessels generated TXA2 in addition to PGI2. The treatment of vascular rings with NTG in concentrations of 5 to 1000 ng/ml and subsequent incubation with AA caused a significant increase in PGI2 in the supernatants, as identified by bioassay (platelet aggregation inhibition) and by measurement of 6-keto-PGF1 alpha (stable hydrolysis product of PGI2). The maximum increase in PGI2 was observed with therapeutic concentrations of NTG, i.e., 5 to 10 ng/ml. The levels of vessel wall-generated TXB2 (stable metabolite of TXA2) were not affected by NTG treatment. A prior incubation of vascular rings with indomethacin abolished the increase in PGI2 after NTG treatment. In contrast, incubation of vascular rings with OKY 1581 (selective TXA2 inhibitor) resulted in a significant additional increase in PGI2 release but no change in TXB2 levels after NTG treatment. These studies indicate important effects of NTG on vascular PGI2 generation but not on TXA2 generation.

Epoprostenol↗
PubMed1983

Inhibitory effects of diltiazem on platelet activation caused by ionophore A23187 plus ADP or epinephrine in subthreshold concentrations.

We examined the effects of the slow channel Ca++ blocker diltiazem on human platelet aggregation and TXA2 generation. Diltiazem inhibited platelet aggregation induced by 2 microM ADP or 5.5 microM epinephrine alone at 5 and 50 micrograms/ml (11.1 and 111 microM), respectively, and that induced by threshold concentrations of ADP or epinephrine at 0.2 to 1.0 micrograms/ml (0.4 to 2.2 microM). Platelet TXA2 generation stimulated by either ADP or epinephrine alone was inhibited by diltiazem in concentrations above the clinically achieved range (0.05 to 0.2 micrograms/ml, 0.1 to 0.4 microM). When PRP was stimulated with subthreshold concentrations of the Ca++ ionophore A23187 followed by subthreshold concentrations of ADP or epinephrine, a marked potentiation of platelet aggregation and TXA2 generation was observed. Incubation of PRP with diltiazem in a pharmacologic range resulted in marked reduction in ionophore A23187-induced potentiation of platelet activity caused by ADP or epinephrine. In other experiments, diltiazem was found to have no effects on PGI2-induced platelet aggregation inhibition. On the basis of these data, we conclude that (1) Ca++ flux across the platelet membrane stimulates platelet activity of subthreshold concentrations of ADP or epinephrine and (2) diltiazem in therapeutic concentrations reduces platelet activation induced by ionophore A23187 plus ADP or epinephrine, most likely by inhibiting Ca++ flux. These effects of diltiazem may not be observed in the therapeutic range if aggregatory concentrations of ADP or epinephrine alone are used.

Adenosine Diphosphate↗
PubMed1983

Spontaneous rupture of splenic artery aneurysm: sixth instance of both maternal and fetal survival.

Spontaneous rupture of a splenic artery aneurysm in the third trimester of pregnancy is a catastrophic event associated with a very high fetal and maternal mortality rate. There are only five reported instances of both maternal and fetal survival after spontaneous rupture of a splenic artery aneurysm. This report not only documents the sixth such case, but also recommends a different therapeutic approach for the management of such cases.

Adult↗
PubMed1982

Comparison of platelet function during exercise in normal subjects and coronary artery disease patients: Potential role of platelet activation in myocardial ischemia.

Platelet function parameters as influenced by exercise stress were evaluated in 22 patients with coronary artery disease (CAD) and in 13 normal subjects. Upon exercise stress, 14 CAD patients exhibited positive tests and eight exhibited negative tests. Platelet counts during exercise increased similarly in normal and CAD patients. Platelet aggregation response to ADP was unaffected by exercise both in normal and CAD patients. Platelets from 7 of the 14 CAD patients with positive stress tests had increased sensitivity to endoperoxide analog (U-46619) defined as less than 200 ng/ml U-46619 required for 50% platelet aggregation. Resting plasma beta-thromboglobulin (B-TG) levels, an index of in vivo platelet activation, were significantly higher in CAD patients compared to normal subjects (74 +/- 7 and 41 +/- 5 ng/ml, respectively; p less than 0.02). During exercise plasma B-TG levels increased in normal subjects to 60 +/- 5 ng/ml. In contrast, B-TG levels increased to 102 +/- 14 ng/ml in CAD patients (p less than 0.01 compared to normal subjects). These increases were transient and B-TG declined to preexercise values soon after exercise. Eleven of the 12 CAD patients with positive exercise stress tests had increases in plasma B-TG levels, whereas only three of the eight CAD patients with negative stress tests had any increase. These observations of increased platelet activation in certain CAD patients during exercise may be related to exercise-induced myocardial ischemia.

Adult↗
PubMed1982

Comparison of umbilical vein models for measurement of relative prostacyclin and thromboxane production.

There is growing evidence that blood vessels generate TXA2 in addition to PGI2. We examined effluents from continuously perfused human umbilical vein and supernatants from umbilical vein rings for TXB2 and 6-keto-PGF1 alpha measurements (stable metabolites of TXA2 and PGI2, respectively). TXB2 and 6-keto-PGF1 alpha were identified in all samples. 6-keto-PGF1 alpha to TXB2 ratio was higher in intact vein effluents than in the venous ring supernatants (112:1 and 28:1, respectively, P less than 0.01). Arachidonate stimulation increased 6-keto-PGF1 alpha and TXB2 levels similarly in the intact vein effluent. In contrast, stimulation of the venous rings resulted in a relatively larger increase in TXB2 than in 6-keto-PGF1 alpha. This caused 6-keto-PGF1 alpha to TXB2 ratio to decline (p less than 0.01). The identity of TXB2 was confirmed in several different ways. These data suggest that 1) human umbilical veins produce TXA2 in addition to PGI2, 2) TXA2 release is more by venous rings than by the intact vein probably reflecting contribution from non-endothelial layers, and 3) arachidonate stimulation causes relatively greater release of TXA2 than of PGI2 from the venous rings, whereas release of PGI2 and TXA2 is similar from the intact vein.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Effect of dipyridamole on prostaglandin generation by human platelets and vessel walls.

These experiments were conducted to determine the effects of dipyridamole on human platelet aggregation, platelet thromboxane A2 (TXA2) and human vessel wall prostacyclin (PGI2) generation. Dipyridamole in varying concentrations (5 to 50 micrograms/ml) had no direct effect on ADP-induced platelet aggregation in vitro, but it potentiated PGI2-induced platelet aggregation inhibition at these concentrations. Dipyridamole also inhibited arachidonic acid-induced platelet TXA2 generation at these concentrations. In continuously perfused umbilical vein segments, dipyridamole treatment resulted in stimulation of PGI2 release determined by bioassay and by measurement of its stable metabolite 6-keto-PGF1 alpha. Minimum concentration of dipyridamole causing PGI2 release was 50 micrograms/ml. These in vitro studies suggest that anti-thrombotic effects of dipyridamole in man are mediated mainly by potentiation of PGI2 activity and to some extent by TXA2 suppression. Stimulation of PGI2 release by human vessels may not be seen in usual therapeutic concentrations.

Arachidonic Acid↗
PubMed1982

Effects of smoking on platelets and on plasma thromboxane-prostacyclin balance in man.

To determine the influence of brief period of smoking on platelet release and platelet-vessel wall prostaglandins, we studied 13 non-smokers and 15 habitual smokers. Blood samples were collected before and immediately after smoking. Before smoking plasma beta-thromboglobulin levels were similar in the two groups. Plasma levels of thromboxane B2 (TXB2), stable metabolite of TXA2 were slightly higher (124 +/- 43 vs 101 +/- 36 pg/ml) and of 6-keto-PGF1 alpha (stable metabolite of PGI2) lower (39 +/- 23 vs 63 +/- 23 pg/ml) in smokers compared to non-smokers. Immediately after smoking, plasma TXB2 levels increased 197% (P less than 0.05) and plasma 6-keto-PGF1 alpha 44% (P-NS) in non-smokers. Similar increases were not observed in the smoker population, although plasma beta-thromboglobulin levels increased 40%. Platelet TXA2 generations induced by arachidonic acid and thrombin were similar in the two groups. These data show that brief period of smoking stimulates both TXA2 and PGI2 release in the non-smokers. Increase in TXA2 is more than in PGI2. Episodic increase in TXA2 may be a mechanism of vascular injury. Absence of increase in TXA2 and PGI2 with smoking in habitual smokers may reflect tolerance to effects of smoking.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Thromboxane and prostacyclin generation by intact human vessels in response to balloon catheter trauma.

Recent description of thromboxane (TXA2) synthesis by endothelial cells in addition to prostacyclin (PGI2) has stimulated interest in the significance of TXA2 generation by vessel walls. We studied TXA2 and PGI2 release from human umbilical veins with intact and continuous endothelium. Resting TXB2 (stable metabolite of TXA2) concentrations in umbilical vein effluent (mean 0.45 +/- 0.07 ng/ml) were lower than those of 6-keto-PGF1 alpha (stable metabolite of PGI2) (mean 92 +/- 26 ng/ml). Following mechanical trauma to the umbilical veins with a balloon catheter, documented by adherence of indium111-labeled platelets, both TXA2 and PGI2 increased in the venous effluent. Increase in TXB2 (65%) was less than that in 6-keto-PGF1 alpha (199%). These data show that a) human vessel walls generate both TXA2 and PGI2, b) both TXA2 and PGI2 increase following mechanical trauma, the former less than the latter. Vessel wall TXA2 generation may become pathologically relevant in conditions of decreased PGI2 generation.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Effects of propranolol therapy on platelet release and prostaglandin generation in patients with coronary heart disease.

Suppression of platelet function is thought to be a mechanism of propranolol's beneficial action in angina pectoris. To study the effects of propranolol on platelets, we measured plasma beta thromboglobulin and plasma thromboxane B2 (TXB2, stable metabolite of TXA2) levels by radioimmunoassay as indexes of platelet alpha-granule and TXA2 release, respectively. Platelet TXA2 generation in vitro in response to arachidonate and thrombin was also quantitated. Twenty-nine patients with coronary disease -- 15 not taking propranolol (group A) and 14 taking propranolol (group B) -- and 15 normal subjects were studied. Plasma beta-thromboglobulin levels were increased in group A and B patients (mean 63 +/- 8 and 96 +/- 14 ng/ml, respectively) compared with normal subjects (mean 46 +/- 6 ng/ml). Plasma TXB2 levels were similar in group A and B patients and in normal subjects (mean 148 +/- 41, 149 +/- 36 and 216 +/- 39 pg/ml). Arachidonate-induced platelet TXA2 generation was significantly higher in group A patients than in normal subjects (725 +/- 393 vs 82 +/- 25 pg TXB2/10(8) platelets, p less than 0.001). In contrast, platelets from group B patients had very low TXA2 generation (mean 21 +/- 18 pg) compared with platelets from group A patients or normal subjects (p less than 0.001). Similar results were obtained using thrombin. These data show that propranolol therapy does not affect platelet-released beta thromboglobulin or TXA2 at rest, but significantly reduces the capability of platelets to generate TXA2 in vitro. Reduction in platelet TXA2 generation may be an important mechanism of action of propranolol in patients with coronary artery disease.

Adult↗
PubMed1982

Prostacyclin and platelet aggregation in sickle cell disease.

Patients with sickle cell disease have been described to have decreased platelet aggregation. The cause of this decrease is believed to be the refractory state of platelets from continual in vivo activation. In this study, plasma 6-keto PGF1 alpha (stable metabolite of vessel wall-derived prostaglandin, prostacyclin) levels were measured to study the mechanism of decreased platelet aggregation. Plasma 6-keto PGF1 alpha levels were measured by radioimmunoassay in ten patients with sickle cell disease and in ten control subjects. Plasma 6-keto PGF1 alpha levels in normal subjects ranged from 0 to 100 pg/ml (mean 40 +/- 14 pg/ml), but were significantly higher in patients with sickle cell disease (range 170 to 880 ng/ml, mean 446 +/- 89 pg/ml, P less than .002). Platelet aggregation in response to an endoperoxide analog in these patients was lower compared with that of the control subjects. This study suggests that prostacyclin activity is increased in subjects with sickle cell disease. This increased activity is probably due to persistent stress to the endothelium from hemolysis and continual platelet activation. Decreased platelet aggregation seen in these patients may be due to elevated prostacyclin activity.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗