Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To elucidate the relationship between the high concentration of taurine in platelets and platelet aggregation in patients with EPH gestosis (gestosis with edema, proteinuria and hypertension), platelet aggregation and the platelet release response (release of ATP and beta-thromboglobulin) were studied in the washed platelet suspension (PS) obtained from normal pregnant or non-pregnant women and EPH gestosis patients. Platelet aggregation and platelet release response were significantly lower in EPH gestosis patients than in normal pregnant and non-pregnant women. Platelet aggregation, platelet release response induced by ADP and collagen and the aggregation induced by A23187 were inhibited in taurine-loaded PS from non-pregnant women. These results suggest that the decrease of platelet aggregation in EPH gestosis patients was caused by high concentrations of taurine in platelets, which may inhibit the intracellular Ca2+ movement and platelet release response. Therefore, taurine appears to have a protective effect against the hyper-coagulative state in EPH gestosis.
 ...
PMID:Effect of taurine concentration on platelet aggregation in gestosis patients with edema, proteinuria and hypertension. 144 48

We have previously shown that the stimulatory effects of guanine nucleotides, N-ethylcarboxamide-adenosine and other agonists on adenylate cyclase activity were diminished in aorta and heart sarcolemma of spontaneously hypertensive rats (SHR) [Anand-Srivastava (1988) Biochem. Pharmacol. 37, 3017-3022]. In the present studies, we have examined whether the decreased response of these agonists is due to the defective GTP-binding proteins (G-proteins) which couple the receptors to adenylate cyclase, and have therefore measured the levels of G-proteins in aorta and heart from SHR and their respective Wistar-Kyoto (WKY) controls by using pertussis toxin (PT)- and cholera toxin (CT)-catalysed ADP-ribosylations and immunoblotting techniques using specific antibodies against G-proteins. The labelling with [32P]NAD+ and PT identified a 40/41 kDa protein in heart and aorta from WKY and SHR and was significantly increased in the hearts (approximately 100%) and aorta (approximately 30-40%), from SHR as compared with WKY. Immunoblotting revealed an increase in the levels of the G-protein alpha-subunits Gi alpha-2 and Gi alpha-3 in heart and Gi alpha-2 in aorta, whereas no change in Go alpha was observed in heart from SHR and WKY. On the other hand, no differences were observed in CT labelling or immunoblotting of stimulatory G-protein (Gs) in heart and aorta from WKY and SHR. In addition, CT stimulated the adenylate cyclase activity in heart sarcolemma from WKY and SHR to a similar extent. These results were correlated with adenylate cyclase inhibition and stimulation by various hormones. Angiotensin II (AII), atrial natriuretic factor (ANF) and oxotremorine-mediated inhibition was found to be greater in SHR as compared with WKY, whereas the stimulatory effects of adrenaline, isoprenaline, dopamine and forskolin were diminished in SHR aorta as compared to WKY. These results indicate that regulatory protein G(i) is more expressed in SHR, which may be associated with the decreased responsiveness of stimulatory hormones and increased sensitivity of inhibitory hormones to stimulate/inhibit adenylate cyclase activity. It may thus be suggested that the enhanced G(i) activity may be one of the mechanisms responsible for the diminished vascular tone and impaired myocardial functions in hypertension.
 ...
PMID:Enhanced expression of inhibitory guanine nucleotide regulatory protein in spontaneously hypertensive rats. Relationship to adenylate cyclase inhibition. 144 83

The effect of 3,4-Dihydroxyacetophenone (DHAP) on platelet aggregation in normal pregnancy and pregnancy induced hypertension (PIH) in the third-trimester was studied by optical method. The IC50 values of DHAP in inhibiting ADP-induced platelet aggregation in normal pregnancy and PIH were 1.0 x 10(-3) mol/L and 2.4 x 10(-3) mol/L respectively. A dose-effect relationship of DHAP was also demonstrated (r greater than 0.92). At various time-phases of ADP-induced platelet aggregation, the addition of DHAP to the platelet-rich plasma could rapidly decrease the two-phase aggregation. DHAP of 200-240 mg/d x 3-5 days by i.v. drips given to patients with PIH also inhibited ADP-induced platelet aggregation. The authors conclude that DHAP is a potent antithrombogenic agent both in vitro and in vivo and is therefore a promising drug to improve utero-placenta-fetal circulation.
 ...
PMID:[Effect of 3,4-dihydroxyacetophenone on platelet aggregation in normal pregnancy and pregnancy induced hypertension]. 150 79

The effect of treatment for eight weeks with isradipine 1.25 mg twice daily for 4 weeks and thereafter 2.5 mg twice daily for 4 weeks on ex vivo platelet function was investigated in 10 male hypertensive patients, aged 51 (6.1) y. Systolic and diastolic blood pressure, platelet aggregation in response to ADP, serum thromboxane B2 and beta-thromboglobulin levels were significantly decreased at rest before exercise ergometry, during exercise and at rest after exercise. The platelet count, platelet sensitivity and the plasma levels of 6-oxo-prostaglandin F1 alpha were not affected by isradipine. It is concluded that a compound that lowers blood pressure and inhibits platelet activation may be of clinical benefit in the routine treatment of hypertension.
 ...
PMID:Isradipine improves platelet function in hypertensives. 153 96

SQ 33,261 ([1S-[1 alpha,2 alpha(Z),3 alpha,4 alpha]]-6-[3-[[2- [(phenylamino)carbonyl]hydrazono]methyl]-7-oxabicyclo[2.2.1]hept-2 - yl]-4-hexenoic acid) and SQ 33,552 ([1S-[1 alpha,2 alpha(Z),3 alpha,4 alpha]]-6-[3-[[[[(4- chlorophenyl)amino]carbonyl]hydrazono]methyl]-7- oxabicyclo[2.2.1]hept-2-yl]-4-hexenoic acid) are potent thromboxane (Tx) A2 receptor antagonists. They inhibited platelet aggregation in platelet-rich plasma induced by the TxA2 mimetic, U-46,619 (10 microM), with IC50 values of 200 and 70 nM, respectively. Neither compound inhibited ADP (20 microM)-induced platelet aggregation (IC50 greater than 1000 microM). SQ 33,261 and SQ 33,552 competitively antagonized U-46,619-induced contraction of rat aortic strips with respective pA2 values of 9.0 and 10.1 and KB values of 1.2 and 0.1 nM. They also competitively antagonized U-46,619-induced contraction of guinea pig tracheal strips with pA2 values of 8.9 and 9.9 and KB values of 1.9 and 0.4 nM, respectively. SQ 33,261 and SQ 33,552 (p.o.) were potent inhibitors of U-46,619 (2 mg/kg i.v.)-induced death in mice with ID50 values of 8 and 1 micrograms/kg, respectively. SQ 33,261 and SQ 33,552 (0.2 mg/kg p.o.), also had long duration of action in this assay with 50% survival times of 7 and 15 hr, respectively. SQ 33,261 at 0.01 and 1.0 mg/kg i.v., inhibited arachidonic acid-induced bronchoconstriction and reversed arachidonic acid-induced hypertension to a hypotensive response. SQ 33,552 inhibited TxA2 synthase at high concentrations (IC50 = 307 microM), whereas SQ 33,261 was inactive. Neither compound inhibited cyclooxygenase or caused an elevation of platelet cyclic AMP levels.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Pharmacological characterization of potent, long-acting thromboxane receptor antagonists, SQ 33,261 and SQ 33,552. 153 33

The goal of this study was to determine the role of prostaglandin H2-thromboxane A2 (PGH2-TxA2) in altered responses of cerebral arterioles during chronic hypertension. Diameter of pial arterioles was measured during suffusion with ADP, acetylcholine, and nitroglycerin using intravital microscopy in Wistar-Kyoto (WKY) normotensive rats and spontaneously hypertensive rats (SHR) (8-10 mo old). ADP (100 microM) increased pial arteriolar diameter by 21 +/- 3% (means +/- SE) in WKY and only by 7 +/- 3% in SHR. Acetylcholine (10 microM) increased diameter 10 +/- 2% in WKY and, in contrast, reduced diameter 7 +/- 3% in SHR. Nitroglycerin produced similar vasodilatation in WKY and SHR. We then examined whether impaired dilatation of cerebral arterioles in SHR to ADP and acetylcholine may be related to activation of the PGH2-TxA2 receptor. SQ 29548, a specific PGH2-TxA2 receptor antagonist, restored vasodilatation in response to ADP in SHR toward that observed in WKY and reversed vasoconstriction to vasodilatation in response to acetylcholine in SHR. SQ 29548 did not alter responses in WKY. Thus these findings suggest that impaired responses of cerebral arterioles to ADP and acetylcholine during chronic hypertension may be related to the activation of the PGH2-TxA2 receptor.
 ...
PMID:Role of prostaglandin H2-thromboxane A2 in responses of cerebral arterioles during chronic hypertension. 153 13

Changes of platelet aggregation in relation to macroangiopathy and to some of its risk factors were observed in microangiopathy-free, well-controlled type 1 diabetic males. Platelet aggregate ratio was generally lower in patients (n = 77) than in age-matched healthy subjects (n = 48). In the absence of cigarette smoking, hypertension, obesity and hypercholesterolemia (n = 25) in vitro platelet hyperaggregation was found induced with epinephrine, collagen or arachidonic acid, and to a lesser degree with ADP. There was no change in the presence of at least one risk factor in addition to diabetes (n = 29), but there was a further significant increase in platelet aggregation when overt coronary, cerebral or peripheral artery disease was present (n = 23).
 ...
PMID:Platelet function in male diabetics with and without macrovascular complications. 156 30

Calcium antagonists have become widely used as antihypertensive treatment in diabetic patients, although data concerning a possible influence on glucose tolerance, insulin secretion, and platelet aggregation during long-term, placebo-controlled studies are lacking. Therefore, the effects of isradipine, a new calcium antagonist, on glucose tolerance and insulin secretion during a 75-g oral glucose tolerance test (OGTT) and on ADP- and collagen-induced maximum first-wave platelet aggregation (Tmax%) were studied in 11 type II diabetic patients with borderline hypertension. After a 2-week washout period, patients were treated with placebo or isradipine for 8 weeks in a double-blind, crossover study. Systolic blood pressure was lowered significantly after isradipine therapy compared to placebo (127 +/- 3 vs. 139 +/- 6 mm Hg; p less than 0.05). Fasting blood glucose (153 +/- 14 vs. 157 +/- 16 mg/dl; NS), glucose levels, and basal (17 +/- 4 vs. 17 +/- 2 mU/ml; NS) and stimulated insulin during the OGTT remained unchanged after either treatment. Platelet aggregation after stimulation with different concentrations of ADP and collagen showed no significant differences. These data indicate that calcium antagonists have no adverse effects on glucose tolerance, insulin secretion, and platelet aggregation in type II diabetes mellitus, and are therefore useful in the treatment of hypertension in diabetic patients.
 ...
PMID:Platelet aggregation and metabolic control are not affected by calcium antagonist treatment in type II diabetes mellitus. 169 14

The effect of various antihypertensive medications on platelet function is of increasing interest. Conflicting effects of captopril on platelet function are reported and the impact of angiotensin converting enzyme (ACE) inhibitors not containing a sulfhydryl group such as enalapril, lisinopril, and quinapril on platelet function remains unstudied. Therefore, the aim of the present study was to examine the effect of antihypertensive treatment with quinapril, a novel ACE inhibitor not containing a sulfhydryl group, on platelet function. Ten white men (age range of 32-61 years) with untreated mild-to-moderate essential hypertension (supine diastolic blood pressure greater than 95 mm Hg) were treated with 4 weeks each of placebo and quinapril in a double-blind, randomized, crossover design. Quinapril (20 mg twice a day) significantly lowered systolic (p less than 0.01) and diastolic blood pressure (p less than 0.01) without any significant effect on heart rate or plasma catecholamines. No significant change was noted for in vitro platelet aggregation induced by epinephrine, ADP, or collagen. Plasma concentrations of the platelet release factors beta-thromboglobulin and platelet factor 4 did not change, nor did the platelet content of norepinephrine, platelet weight (mg/10 ml of blood), circulating platelet count, or platelet size. Thus, as assessed by a broad spectrum of platelet parameters, we found that antihypertensive treatment with quinapril has no significant effect on platelet function in patients with mild-to-moderate essential hypertension. These "platelet-neutral" properties of quinapril suggest that quinapril, both from a thromboembolic and a hemostatic point of view, may be a rather safe agent for treatment of hypertension.
 ...
PMID:Platelet function during antihypertensive treatment with quinapril, a novel angiotensin converting enzyme inhibitor. 170 46

Both marked hypercholesterolemia and severe hypertension have been reported to be associated with an enhanced sensitivity of blood platelets to activating agents. To investigate a possible mutual synergistic effect of moderate hypercholesterolemia and mild hypertension on platelet reactivity, we studied in 29 patients the response to aggregating agents, ADP and collagen, and the intracellular cyclic AMP content and cytosolic Ca2+ concentration that participate, respectively, as inhibitory and stimulatory mediators in platelet responses. When compared to age- and blood pressure-matched patients with normal or slightly elevated plasma cholesterol, the patients with total platelet cholesterol higher than 6.4 mM were characterized by a decreased response to collagen and ADP (14.5 +/- 3.0 vs. 23.8 +/- 2.0 a.u. and 17.7 +/- 4.5 vs. 26.9 +/- 2.7 a.u., respectively), a tendency to a reduced cAMP content both in the basal state and after phosphodiesterase inhibition by Ro-15 2041 (2.83 +/- 0.18 vs. 3.26 +/- 0.22 mumol/10(8) cells and 4.57 +/- 0.29 vs. 5.38 +/- 0.36 mumol/10(8) cells, respectively), and no change in cytosolic Ca2+ concentration (190 +/- 11 vs. 203 +/- 13 nM). After a chronic treatment with nitrendipine (20 mg/day for 6 months), blood pressure, platelet [Ca2+]i and cAMP content decreased in the patients with normal or moderately elevated hypercholesterolemia (p less than 0.001, less than 0.001, and less than 0.05, respectively), but these effects were attenuated or absent in the patients with higher hypercholesterolemia. Plasma lipids and the platelet-aggregating response to ADP and collagen were unchanged by this long-term nitrendipine treatment in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Hypercholesterolemia modulates the effects of nitrendipine on blood pressure and platelet function in essential hypertension. 172 3


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>