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

Two of the many mediators synthesized by vascular endothelial cells (EC), are involved in maintaining the surface of the normal, healthy endothelium in a non-thrombogenic state. The first is prostacyclin, a product of arachidonic acid metabolism, discovered in 1976. This labile prostanoid, with a half life of approximately 3 minutes, relaxes vascular smooth muscle and inhibits the aggregation of blood platelets. Prostacyclin and its analogues are currently being tested in the clinic for cardiovascular diseases such as primary pulmonary hypertension. A number of drugs including defibrotide, nafazatrom, ronicol and cicletanine may exert their therapeutic effects by releasing prostacyclin from the EC. The second mediator discussed is endothelium-derived relaxing factor (EDRF), discovered in 1980, which also relaxes smooth muscle and inhibits the aggregation and adhesion of platelets. Substances which stimulate release of EDRF include acetylcholine, bradykinin and ADP. EDRF is even more labile than prostacyclin with a half life counted in seconds. It has recently been identified as nitric oxide formed from L-arginine by an unknown mechanism. Prostacyclin and EDRF are released together following stimulation of endothelial receptors and synergize to inhibit platelet aggregation. It is suggested that these mediators form the endothelial defence mechanism against blood-borne cells and chemicals and that breakdown of this barrier results in diseases such as hypertension and atherosclerosis. The peptide, endothelin is the third mediator under discussion. Characterised and synthesised in 1988, it is the most potent vasoconstrictor so far discovered. Three isomers of endothelin have been identified. Paradoxically, endothelin strongly releases both prostacyclin and EDRF thus modulating its own vasoconstrictor actions.
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PMID:Vasoactive mediators derived from the endothelium. 251 50

Abnormal platelet function may contribute to the complications of essential hypertension. We have studied the kinetics of platelet aggregation induced by adenosine diphosphate (ADP) or epinephrine, plasma beta-thromboglobulin, and basal, cytosolic, and free calcium, as correlates of platelet function. Fifteen untreated patients with essential hypertension and without detectable atherosclerosis, 18-40 years old, were compared with 30 matched normotensive control subjects. Maximal rates of platelet aggregation (Vmax) with ADP and epinephrine were significantly higher in patients than in control subjects (p less than 0.03), as assessed by quenched-flow aggregometry. However, significance was lost when Vmax was corrected for the platelet count. Paradoxically, the activation constants (Ka) for ADP were higher in patients than in control subjects (p less than 0.03). With ADP as the inducing agent, onset time (t) or lag period before aggregation begins was longer in patients than in control subjects (p less than 0.02). beta-thromboglobulin levels, an index of in vivo platelet activation, were not significantly different between the two groups (p = 0.13). The mean platelet cytosolic free calcium concentration was higher in patients (213 +/- 19 nM) than in control subjects (172 +/- 14 nM), but this difference was not statistically significant (p = 0.07). However, there was a close correlation between the free calcium level and systolic, diastolic, and mean blood pressure (p less than 0.003, p less than 0.04, p less than 0.004, respectively). No difference in platelet volume between the two groups was found. Our data suggest that platelets in the early stages of essential hypertension display an overall increased aggregation potential but a diminished sensitivity to ADP.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1989 Jun
PMID:Platelet calcium and quenched-flow aggregation kinetics in essential hypertension. 252 22

Abnormal activation of blood platelets may be a contributory factor in the accelerated vascular disease which occurs in hypertension. We investigated the effects of lowering blood pressure in 12 patients with mild hypertension on several aspects of platelet function, initially in a placebo-controlled, double-blind, cross-over study with nisoldipine, and subsequently in the same patients comparing nisoldipine with the patients' usual anti-hypertensive therapy. Values were compared with those from an age, sex-matched control population. Seven hypertensive patients with renal failure were also studied. Administration of nisoldipine reduced ex vivo "spontaneous" aggregation of blood platelets significantly, and a similar significant effect was seen when blood pressure was lowered by the patients usual anti-hypertensive therapy. "Spontaneous" aggregation occurring in the control population was similar to that in the treated hypertensives. Blood platelet count, and aggregation in response to ADP and adrenalin were unaffected by treatment. Median plasma beta thromboglobulin levels were significantly higher in the untreated hypertensive patients (43 ng ml-1) than in the controls (30 ng ml-1), and there was a trend to reduced values for beta thromboglobulin on treatment of the hypertension. These results indicate that blood platelet activity is enhanced in hypertension and that function returns towards normal when blood pressure is lowered by treatment.
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PMID:Anti-hypertensive drugs non-specifically reduce "spontaneous" activation of blood platelets. 253 78

Treatment of mild to moderate hypertension does not result in any obvious reduction in the frequency of coronary heart disease (CDH) whereas the frequency of cerebrovascular disease is reduced. Platelet activation assumes a central role in the development of arteriosclerosis which is presumed to be the basis of coronary heart disease. Platelet activation may occur at sites of damaged endothelium (eg in the arteriosclerotic plaque) and by means of influencing specific thrombocyte receptors. The receptors may also be activated in vitro, which may be utilized experimentally. By means of stratification of material from the literature, it appears possible that patients with high mean arterial blood pressures (MAP) (over approximately 120 mmHg) have an increased tendency to platelet aggregation for ADP and adrenalin. This hyper-aggregability appears to be related to the blood pressure as it is normalized when MAP is reduced by treatment to values around 120 mmHg. If MAP is under 120 mmHg already, no further decrease in the tendency to platelet aggregation occurs. Some investigations suggest an effect on ischaemic heart disease on treatment of the most hypersensitive patients. The observations quoted in the present article are in agreement with the theory that thrombocyte aggregation may be of significance for development of CDH.
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PMID:[Platelet function, hypertension and ischemic heart disease]. 267 54

Patients with transient ischemic attack (TIA) in the vertebrobasilar artery more often complain of disturbance of equilibrium, such as vertigo or dizziness, than of auditory disorders, such as hearing impairment or tinnitus. The author induced TIA in rabbits by injecting adenosine diphosphate (ADP) into the right vertebral artery. Observations of rotatory nystagmus have shown that a peak level of directional preponderance appeared 1 minute after injection of ADP (0.3mg/kg b.w.) and continued for more than 4 minutes. On the other hand, the amplitude of auditory brainstem responses (ABRs) presented no significant changes following the injection of ADP (0.5mg/kg b.w.). However, greater amounts of ADP (1.0 and 2.0 mg/kg b.w.) were found to reduce the amplitude of ABR-waves, although significant reduction was observed for only less than 1 minute. This change was represented by flattening of the later part of the waves, with the first wave much less affected. Electrocochleogram (E. Coch. G.) have also demonstrated a transient reduction in amplitude 10 seconds after injection of ADP (4.0mg/kg b.w.) with correspondingly rapid recovery. In cases of hypertension due to noradrenaline load or trimethaphan-induced hypotension, reduced amplitudes were more profound and continued longer, returning to its normal range within 1 minute. Differences in susceptibility between the equilibrium system and auditory system in TIA of the vertebrobasilar artery are discussed.
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PMID:[Difference in susceptibility between auditory and equilibrium function in rabbits with experimentally-induced transient ischemic attack]. 274 23

The area postrema is a circumventricular organ that plays an important role in neurohumoral regulation of the circulation. We have developed a method to examine permeability and vascular responses of the microcirculation of the area postrema in vivo. A craniotomy was performed over the dorsal brain stem in anesthetized rats, and blood vessels to the area postrema were visualized with fluorescein microscopy. Extravasation of sodium fluorescein (MW, 386), but not 150 kDa (MW) fluorescein isothiocyanate-dextran, occurred in the area postrema under control conditions. There was no extravasation of fluorescein or dextran in the brain stem under control conditions. Acute hypertension produced marked disruption of the barrier to 150 kDa dextran in the area postrema, compared with minimal disruption in the brain stem. We tested the hypothesis that the area postrema has greater permeability to small molecules than the brain stem and that this permeability might be accompanied by distinctive vascular responses. Topical suffusion of adenosine and ADP produced similar dose-related dilation of arterioles to area postrema and dorsal brain stem. Topical and intravenous vasopressin produced similar dose-related constriction of vessels to area postrema and brain stem. Electron microscopy in rats demonstrated that a barrier to horseradish peroxidase, which is absent in capillaries in the area postrema, is present in arterioles that supply the area postrema.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Microcirculation of the area postrema. Permeability and vascular responses. 275 49

The authors studied thrombin-induced aggregation of blood platelets washed clean of plasma and some parameters of their energetic status (content of ATP, ADP, and glycogen) in rats with acute vasorenal hypertension (AVH). Sensitivity of platelets to thrombin, the inductor of aggregation, was found to be increased and the initial aggregation in rats with AVN accelerated as compared to that in the controls. At the same time, the total adenine nucleotide content in platelets of rats with AVH was reduced--the ATP content by 33% and the glycogen content by 27%. The data obtained provide evidence that there is no correlation between the ATP and glycogen content in rat platelets and their ability for aggregation.
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PMID:[Aggregation of blood platelets and their energetic status in acute arterial hypertension]. 279 3

Platelet activation factor (PAF)-, ADP and vasopressin-induced increments of platelet Ca2+ concentration were measured by quin-2 in 64 patients with essential hypertension and 16 normal donors. Basal concentration of free Ca2+ was 87 +/- 4 nM in donors, 106 +/- 5 nM in patients with labile hypertension (LH) and 122 +/- 6 nM in those with stable hypertension (SH) (p less than 0.01). PAF, ADP and vasopressin, added to platelets, increased [Ca]in by 448 +/- 58, 397 +/- 66, and 277 +/- 50 nM, respectively, in the donors, by 473 +/- 57, 479 +/- 54 and 195 +/- 32 nM, in LH patients, and by 607 +/- 85, 584 +/- 73 and 245 +/- 41 nM in SH patients. There were no significant variations between the three samples, using the ANOVA test. In 20 patients, whose both parents had essential hypertension, [Ca]in increment was 738 +/- 8 nM for PAF, 682 +/- 90 nM for ADP, and 320 +/- 61 nM for vasopressin. In 19 patients, who admitted to no essential hypertension in the family, these parameters were significantly lower: 310 +/- 40 nM for PAF, 389 +/- 61 nM for ADP, and 147 +/- 26 nM for vasopressin. The demonstrated changes may be making an important contribution to the maintenance of elevated vascular tone and provide an evidence in favor of a genetically-predetermined EH variety.
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PMID:[Receptor-dependent regulation of the concentration of Ca2+ in the cytoplasm of thrombocytes in hypertensive patients]. 284 37

Increased responses to intravenous injections of the full alpha 2-adrenoceptor agonists, alpha-methyl noradrenaline and noradrenaline, were observed in conscious rabbits with perinephritis hypertension. However, responses to the partial agonist, BHT 920, and the antagonist, idazoxan, were unchanged. These increased responses to noradrenaline and alpha-methyl noradrenaline did not appear to be related to the alpha 1- or beta-adrenoceptor activity or to altered clearance of the agonists. The pro-aggregatory response of platelets from hypertensive rabbits and normotensive rabbits to adenosine diphosphate (ADP) was similar, but the sensitivity of platelets from hypertensive rabbits to the adrenaline potentiation of the pro-aggregatory response was increased. This was not related to changes in the number of alpha 2-adrenoceptor binding sites or to changes at platelet beta-adrenoceptors. In contrast the aggregatory responses to the partial agonist, guanabenz, were similar in normotensive and hypertensive animals. In rabbits with perinephritis hypertension responses to phenylethanolamines (full agonists at the alpha 2-adrenoceptor) were increased in vivo in the conscious animal and in vitro in platelets, whereas responses to imidazolines which are partial agonists were similar in normotensive and hypertensive animals. These differences may be related to alterations in the coupling of alpha2-adrenoceptor activation to response in the hypertensive rabbits.
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PMID:Studies on alpha 2-adrenoceptors in rabbits with perinephritis hypertension. 287 Jan 19

The major findings of a review of the literature on platelet aggregation in hypertensive human subjects and the effects of antihypertensive agents were as follows: (1) There is an increased platelet aggregatory response to epinephrine and ADP in hypertensives with MAP greater than 120 mmHg. (2) Treatment with propranolol decreases the aggregatory response to ADP, but it may enhance the response to epinephrine. (3) Treatment with calcium blockers in normotensives decreases the aggregatory response to epinephrine. Further work needs to be done to answer the questions raised by this review. Since the major goal, yet unachieved, of antihypertensive therapy is reduction of the incidence of CHD, the anti-thrombotic or thrombotic potential of antihypertensive agents must be known. Future clinical trials of drug therapy for hypertension should be designed to include at least a determination of platelet aggregation in response to both ADP and epinephrine.
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PMID:Platelet aggregation in hypertension and the effects of antihypertensive treatment. 289 88


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