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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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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)
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PMID:Hypercholesterolemia modulates the effects of nitrendipine on blood pressure and platelet function in essential hypertension. 172 3

In 80 patients with moderate hypertension the effects of nisoldipine 10 mg b.i.d., nifedipine 10 mg and 20 mg t.i.d., diltiazem 60 mg and 120 mg t.i.d., and verapamil 40 mg q.i.d. (all after single dose and 14 days' treatment) on blood pressure; hemodynamic parameters (cardiac output, stroke volume, left ventricular ejection fraction, and total peripheral resistance); and red blood cell and platelet functional state parameters (platelet aggregation, erythrocytal mechanical resistance, and free hemoglobin and ADP levels in plasma) were studied. All of the drugs studied in doses mentioned produced statistically significant hypotensive effects. Nifedipine 20 mg and nisoldipine 10 mg produced the most peripheral vasodilatator activity after a single dose and chronic treatment. Diltiazem had the same effect only in doses of 120 mg and after chronic treatment. However, all the drugs significantly normalized the red blood cell and platelet functional state disturbances in 70-80% of patients with moderate hypertension, even 2 h after a single dose. Disaggregation effect was parallel to clinical improvement. These data make it possible to predict the individual response of most patients to antihypertensive drugs on the basis of acute pharmacological tests, with determination of disaggregation effect.
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PMID:The effects of nisoldipine, diltiazem, nifedipine, and verapamil on hemodynamic parameters and red blood cells-platelet interactions in patients with arterial hypertension. 172 40

Platelet function was investigated in healthy volunteers and patients with essential hypertension by measurement of thresholds for ADP and adrenaline-induced aggregation and plasma concentrations of platelet factor 4 (PF-4) and beta-thromboglobulin (beta-TG) after administration of antihypertensive drugs. Fibrinolytic activity was investigated by the euglobulin clot lysis time (ECLT) and tissue plasminogen activator (t-PA) activity. Compared to normotensive controls, patients with essential hypertension showed increased aggregation as evidenced by a decrease in ADP thresholds for ex vivo platelet aggregation. ECLT was significantly prolonged and t-PA significantly lowered, indicating impaired fibrinolytic activity in mild hypertension. In different studies, we have shown that various antihypertensive drug regimens differ in their effects on platelet function and fibrinolytic activity when given to healthy volunteers or patients with mild-to-moderate essential hypertension. In normal volunteers, treatment with the calcium antagonists verapamil, nifedipine, and felodipine lowered plasma concentrations of PF-4 and beta-TG, indicating a reduced platelet activity in vivo. Fibrinolytic activity was not influenced by calcium antagonist treatment in the normal volunteers. Interestingly, however, t-PA increased significantly in the hypertensive group. When compared to placebo or beta 1-selective blockers, propranolol, a non-selective beta-adrenergic blocker without partial agonist activity, reduced ADP and adrenaline threshold values for ex vivo platelet aggregation in hypertensive subjects and impaired fibrinolytic activity in the normal volunteers as well as in the hypertensive groups by increasing ECLT and reducing t-PA. Hypothetically, the effects of antihypertensive drugs on platelet function and fibrinolytic activity could be of importance for their proposed actions on cardiovascular morbidity and mortality.
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PMID:Platelet function and fibrinolytic activity in hypertension: differential effects of calcium antagonists and beta-adrenergic receptor blockers. 172 42

Norepinephrine-induced responses in isolated perfused mesenteric vascular bed from normotensive and renovascular hypertensive rats were examined in the presence of adenosine diphosphate (ADP, 2 x 10(-6) M). Responses to norepinephrine were significantly greater in vessels from hypertensive rats. Norepinephrine-induced contractions increased after the removal of endothelium. N omega-Nitro-L-arginine (L-NOARG), a potent inhibitor of nitric oxide formation, similarly increased contractions. The greatest responses were obtained, however, after treatment of the vascular segments with methylene blue. The presence of ADP caused significant endothelium-dependent decreases in contractions. Although decreases caused by ADP in vessels with endothelium after treatment with L-NOARG were not statistically significant, a tendency to decreased responses seems to suggest that L-NOARG diminishes but does not completely prevent the effect of ADP in mesenteric vessels. Methylene blue partially reduced the endothelium-dependent ADP-induced relaxant effects in sham-operated nephrectomized rats. A tendency to increased contractions to norepinephrine was observed in the presence of ADP after removal of endothelium. Thus, in the mesenteric resistance arteries of the rat under stimulation by ADP, it appears that nitric oxide released from L-arginine and the activity of soluble guanylate cyclase account only in part for the endothelium-dependent decreased responses to norepinephrine. When nitric oxide formation or soluble guanylate cyclase activity are depressed simultaneously with endothelium damage, ADP released from platelets or red blood cells may be an important factor that acts synergically with vasoconstrictor stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Feb
PMID:Endothelium-dependent and endothelium-independent effects of adenosine diphosphate in renovascular hypertension. 173 85

Systemic infusion of angiotensin II, a potent agonist, using doses that are initially subpressor, eventually produces sustained blood pressure elevation and reductions in glomerular capillary ultrafiltration coefficient characterized by enhanced signal transduction to angiotensin II and other agonists. In this setting, there is a significant increased affinity of angiotensin II binding to smooth muscle and glomerular mesangial receptors and enhanced sensitivity and magnitude of angiotensin II-induced decrements in cyclic AMP. Since G proteins are important modulators of binding and signal transduction, the present studies were designed to test the hypothesis that differences in the relative amounts of G proteins may be present and have accounted for differences observed. G proteins were identified and quantitated by isoelectric focusing/sodium dodecyl sulfate-polyacrylamide gel electrophoresis, radiolabeling in the presence of activated toxins with [gamma-32P]NAD+, immunoprecipitation, and immunoblotting. A 168% and 465% increase in pertussis toxin-catalyzed ADP ribosylation of alpha 40-41 was found in angiotensin II-treated groups over control groups for glomerular and mesenteric membranes, respectively. Immunoblotting revealed a 250% and 35% increase in the levels of the Gi isoforms alpha i-2 and alpha i-3, respectively, and a decrease of 53% in alpha i-1 from the angiotensin II-treated group. No differences were observed in cholera toxin labeling or immunoblotting of Gs. These results demonstrate multiple mechanisms whereby angiotensin-induced signal transduction can be modulated involving both the receptors and G proteins. These observed differences in G proteins in systemic and renal vasculature accompanying angiotensin II infusion suggest the possibility of a regulatory role in the pathophysiology of angiotensin II-induced hypertension and renal disease.
Hypertension 1992 Feb
PMID:Angiotensin II-induced changes in guanine nucleotide binding and regulatory proteins. 173 48

To evaluate the ex-vivo effects of labetalol, at effective vasodepressor doses, on platelet aggregation in hypertension, 30 hypertensive patients were randomized to either a labetalol or control group in a ratio of two to one. For the labetalol group, the dosage was titrated from 400 mg to 600 mg per day to achieve a fall of 10 mmHg in mean arterial pressure (MAP). No drug was used in the control group. The study lasted for 4 to 8 weeks. At the beginning and end of the study, platelet aggregation to collagen, adenosine diphosphate and epinephrine were measured according to Born's method. In contrast to the significant reduction in MAP, platelet aggregation was not altered by labetalol compared with the control group. Our data do not support the hypothesis that labetalol, at effective vasodepressor doses, inhibits platelet aggregation in mild-to-moderate hypertensive patients.
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PMID:Lack of effect of labetalol on platelet aggregation in hypertensive patients. 174 39

An in vitro assay was used to investigate the effects of doxazosin on the platelet aggregation induced by epinephrine, collagen, and adenosine diphosphate. Platelet-rich plasma from normotensive subjects and patients with hypertension was compared. Doxazosin produced a concentration-dependent inhibition of platelet aggregation in both groups, but significantly lower concentrations were required to inhibit platelet aggregation in plasma taken from patients with hypertension. The concentrations of doxazosin that inhibited platelet aggregation in vitro were similar to those that are used clinically to control blood pressure in patients with hypertension.
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PMID:The effect of doxazosin on platelet aggregation in normotensive subjects and patients with hypertension: an in vitro study. 182 65

Twelve patients with mild hypertension were compared, after 14 days of placebo, with an age- and gender-matched group of 12 healthy volunteers for platelet aggregability and fibrinolytic activity. Following this, 10 of the 12 hypertensives were treated with the calcium antagonist isradipine for 12 months. Blood was drawn for determinations of platelet aggregation and fibrinolytic activity after two weeks and 12 months of treatment. Platelet aggregation tended to increase in the hypertensives compared with controls, indicated by a lowering of the adenosine diphosphate (ADP) threshold value for irreversible aggregation. Tissue-plasminogen activator (t-PA) activity was significantly decreased in hypertensives compared to controls (P less than .05). During therapy, platelet aggregation decreased and t-PA activity increased (P less than .05). The present data suggest that fibrinolytic activity is decreased and platelet aggregation increased in mild hypertension. Besides the blood pressure-lowering effect, isradipine may protect against thromboembolic diseases by modifying platelet function and fibrinolytic activity.
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PMID:Decreased fibrinolytic activity and increased platelet function in hypertension. Possible influence of calcium antagonism. 182 12

The effects of eight weeks of treatment with isradipine (1.25 mg twice daily for four weeks, followed by 2.5 mg twice daily for four weeks) on ex vivo platelet function were investigated in ten male patients with hypertension. Systolic and diastolic blood pressures, platelet aggregation in response to adenosine diphosphate (ADP), serum thromboxane B2, and beta-thromboglobulin levels were significantly decreased (P less than .05) at rest before exercise ergometry, during exercise, and at rest after exercise. The platelet count and plasma levels of 6-oxo-prostaglandin F1 alpha (PGF1 alpha) were not affected by isradipine. It is concluded that treatment of hypertension with a compound that lowers blood pressure and inhibits platelet activation may be of clinical benefit when routinely applied in hypertensive patients.
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PMID:Effects of isradipine on platelet function in hypertension at rest and during exercise. 182 15


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