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

We assessed the responsiveness of rat juxtamedullary afferent arterioles to purinergic stimulation using the in vitro blood-perfused juxtamedullary nephron technique combined with videomicroscopy to allow direct measurement of arteriolar inside diameter. To minimize the contribution of endogenously formed angiotensin II, all rats were pretreated with enalaprilat (2 mg i.v.) for 30 minutes before the right kidney was isolated and prepared for study. Renal perfusion pressure was set at 110 mm Hg and held constant. Afferent arteriolar diameter averaged 20.9 +/- 0.8 microns (n = 41) under control conditions. Exposure to 1.0 microM 2-chloroadenosine induced a significant (11.1 +/- 3.2%) reduction in vessel diameter, whereas a 100 microM concentration induced an afferent vasodilation (7.6 +/- 1.5%; p less than 0.05). These data are consistent with the preferential stimulation of high affinity constrictor adenosine receptors (A1) at lower concentrations and activation of lower affinity vasodilator adenosine receptors (A2) at higher concentrations. In contrast, ATP elicited a significant afferent vasoconstriction of approximately 9.2%, 12.9%, and 10.0% at concentrations in the range of 1-100 microM (p less than 0.05). Treatment with ADP, at concentrations up to 100 microM, failed to alter vessel caliber significantly. Furthermore, the nonhydrolyzable ATP analogue alpha,beta-methylene ATP produced a rapid and potent vasoconstriction, which mimicked the response to ATP. These data reveal the presence of both adenosine-sensitive P1 and ATP-sensitive P2 purinergic receptors on rat juxtamedullary afferent arterioles and demonstrate that ATP can induce afferent arteriolar vasoconstriction directly without first requiring hydrolysis to adenosine.
Hypertension 1991 Jun
PMID:Juxtamedullary afferent arteriolar responses to P1 and P2 purinergic stimulation. 204 47

In addition to preserving the permselectivity of the vascular wall and providing an antithrombogenic surface, the vascular endothelium contributes importantly to the regulation of vasomotor tone. Indeed, the endothelium participates in the conversion of angiotensin I to angiotensin II; the enzymatic inactivation of several plasma constituents such as bradykinin, norepinephrine, serotonin, and ADP; and the synthesis and release of vasodilator substances such as prostacyclin and the recently discovered endothelium-derived relaxing factor (EDRF). The diffusible EDRF released from the endothelium is nitric oxide or a substance closely related to it such as nitrosothiol. The endothelium also synthesizes and releases vasoconstrictive factors, including products derived from arachidonic acid metabolism and the recently discovered peptide endothelin. An increasing body of evidence from experimental and clinical studies indicates that EDRF and endothelium-derived contracting factors play an important role in vascular physiology and pathology. It has become apparent that the balance of these factors may be a major determinant of systemic and regional hemodynamics. Moreover, through generally opposite effects on growth-related vascular changes, contracting factors such as endothelin and relaxing factors such as EDRF also may be important determinants of the vascular response to injury in various disease states such as atherosclerosis and hypertension. It is clear that the vascular endothelium is a complex and dynamic organ. Understanding endothelium function in normal physiology and disease states is of potential clinical importance and should be the focus of future investigation.
Hypertension 1991 Jun
PMID:Role of endothelium-derived relaxing factor in regulation of vascular tone and remodeling. Update on humoral regulation of vascular tone. 204 72

Effects of vitamin E on platelet function and serum lipid peroxide levels were investigated in DOCA-salt hypertensive rats. In the hypertensive rats, ADP- and collagen-induced platelet aggregation in whole blood were markedly attenuated and accompanied by a reduction of serotonin content as compared with the normotensive controls. These facts indicated the appearance of exhausted platelets, which have already been activated in vivo, due to the hypertension. Platelet vitamin E levels were decreased by 50%, while serum lipid peroxide levels were increased 3.6-fold in the hypertensive rats. Vitamin E administration (10 times the dietary intake) during the experimental periods did not influence either the aggregability or the serotonin content of platelets from the hypertensive rats. However, vitamin E administration significantly prevented the elevation of serum lipid peroxides due to the hypertension. These results suggest that vitamin E administration has little effect on platelet activation in vivo due to DOCA-salt hypertension.
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PMID:Effects of vitamin E administration on platelet function and serum lipid peroxides in DOCA-salt hypertensive rats. 205 24

In various models of hypertension of genetic origin, a hypersensitivity of phospholipase C has been demonstrated to participate in the hyperreactivity of platelets toward a variety of vasoactive agents. Since this abnormality could not be observed in the absence of cell stimulation, it could not account for the increase in free Ca2+ which has been reported in resting platelets in primary hypertension. Likewise, in hypertensive subjects, platelets behave hyperactive when stimulated by ADP, although the stimulus has been demonstrated to be a poor activator of phospholipase C. In order to gain insight into the membrane alteration that could account for the cellular hyperactivity which characterizes hypertensive subjects, we investigated, in resting platelets, the kinetics of radioactive labeling of major membrane phospholipids. Isolated platelets were prepared from SHR (4w and 17w of age), SHR-SP, Dahl salt-resistant and salt-sensitive rats fed either a low or a high salt diet, DOCA-salt hypertensive rats and from the appropriate normotensive controls. Irrespective of the radioactive precursor used (32P-orthophosphate, 3H-glycerol, 3H-choline), the labeling of phosphatidylcholine (PC) was markedly (up to 20 fold) enhanced in SHR (whichever their age) and SHR-SP compared with WKY. This increase, specific of PC, could not be accounted for by differences either in the actual amount of PC or in the uptake of various labels, suggesting an increased PC turnover. Such an increase was also observed in platelets of Dahl hypertensive rats but not in those of DOCA-salt hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Membrane abnormalities and cellular hyperreactivity in different models of hypertension]. 212 54

Lowering blood pressure is not totally effective in preventing the atherosclerotic complications of systemic hypertension. In hypertensive patients both platelet hyperaggregation and dyslipidemia have been suggested as important risk factors. The effect of 8 weeks' treatment with ketanserin on blood pressure, serum lipid parameters (cholesterol, triglycerides, LDL, HDL-C, apolipoprotein A1 and B) and platelet aggregation, induced by collagen, ADP, arachidonic acid, was evaluated in 10 patients with essential hypertension. Ketanserin was effective in lowering blood pressure in all patients, 6 of whom became normotensive. Both CHOL and TG levels and APO B were significantly reduced, whereas HDL-C and APO A1 were significantly increased after treatment. These results might be attributed to the antagonistic activity of ketanserin on alpha-1 adrenoceptors with a consequent inhibition of phosphodiesterase. Platelet aggregation, after stimulation with collagen and arachidonic acid, was significantly reduced secondary to the inhibition of intraplatelet serotonin synthesis and release. These results suggest that keranserin is effective in reducing blood pressure and in achieving normal serum lipid pattern and platelet aggregation. Therefore, this drug might be helpful in controlling the main risk factors for cardiovascular damage.
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PMID:Effects of ketanserin administration on lipid metabolism and platelet aggregation in hypertensive patients. 227 4

Functional and morphological studies were done in three groups of male Sprague-Dawley rats after removal of the right kidney and infarction of approximately five-sixths of the left. Group 1 received no specific therapy. Group 2 was treated with ticlopidine, 150 mg/kg per os, for 50 days starting 10 days after surgical ablation. Group 3 was given the thromboxane antagonist, GR 32191, 3 mg/kg b.i.d. orally for 50 days, like ticlopidine. Untreated Group 1 rats developed renal insufficiency, systemic hypertension, progressive proteinuria and glomerulosclerosis. In Group 2 treatment with ticlopidine was associated with less severe impairment of renal function. Proteinuria was significantly lower and animals were partially protected from the development of glomerulosclerosis. These animals had significantly prolonged skin bleeding time. In vitro ADP and arachidonic acid (AA)-induced platelet aggregation was inhibited. Systemic blood pressure was significantly lower than in controls. In Group 3 rats GR 32191 failed to influence progressive proteinuria and severity of glomerulosclerosis which were comparable to those in Group 1. Bleeding time was not prolonged, and in vitro platelet aggregation was inhibited only when AA was used as aggregating agent. Systemic blood pressure was not influenced. These studies suggest that a drug like ticlopidine, which has a broad spectrum of pharmacological actions on platelets and platelet-cell interactions, does retard the development of progressive renal injury when nephron number is reduced. Specific blocking of thromboxane A2 (TxA2) biological activity does not influence progressive renal disease in rats with remnant kidney.
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PMID:Ticlopidine prevents renal disease progression in rats with reduced renal mass. 231 81

Serotonin is a vasoactive substance that acts on blood vessels and platelets but whose primary action lies in its role as an amplifier for other agents. The aim of this work was to study the effects on blood platelets and erythrocytes of the S2-serotonergic receptor antagonist ketanserin. Twenty-seven patients with untreated hypertension and/or intermittent claudication received a bolus intravenous (i.v.) injection of 10 mg ketanserin followed by 2 mg/h during 3 h i.v. infusion. Platelet function and erythrocyte filterability were studied before and 30 min, 3 h, and 24 h after the bolus injection. The results showed decreases of plasma beta-thromboglobulin and platelet factor 4 levels (p less than 0.001) and platelet aggregation induced by epinephrine plus serotonin (p less than 0.001), whereas ADP-induced aggregation remained unchanged 30 min and 3 h after ketanserin administration. Red cell filterability was decreased (p less than 0.01). There was a tendency toward lower mean arterial blood pressure but heart rate remained unchanged. The dual effect of ketanserin on platelet function and erythrocyte filterability might be of great clinical value in hypertension and peripheral vascular disease in which microcirculatory flow is altered.
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PMID:Effects of ketanserin on platelet function and red cell filterability in hypertension and peripheral vascular disease. 241 53

Plasma beta-thromboglobulin (beta TG) and platelet factor 4 (PF4) were significantly higher in a group of 116 hypertensive men than in a normotensive group of 142 men. They increased with the stage of hypertension but the level did not correlate with the age of the subjects. Platelet aggregation was similar in the two groups and positively correlated with the age of the subjects in the normotensive group but not in the hypertensive group. A strong positive correlation was observed between the levels of plasma beta TG and PF4 and between platelet aggregation to ADP and that to epinephrine in both the hypertensive and normotensive groups. However, there was no correlation between the level of plasma beta TG or PF4 and platelet aggregation. Plasma antithrombin III was lower in the hypertensive group than in the normotensive group. These studies suggest that plasma levels of beta TG and PF4 are closely related to the stage of hypertension and are better indicators than aggregation of in vivo platelet activation in hypertensive subjects. Enhanced platelet activation may be involved in the acceleration of hypertensive arteriovascular damage and atherosclerosis.
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PMID:Plasma concentrations of platelet-specific proteins in different stages of essential hypertension: interactions between platelet aggregation, blood lipids and age. 241 54

Arterial tissue has been analysed by 31P-, 13C-, 23Na- and 1H-NMR spectroscopy. Rabbit thoracic aortas were mounted on a system with perfusate circulation and studied in basal conditions. Phosphorus spectra remained stable for hours and showed low levels of phosphocreatine (PCr) compared to skeletal, cardiac or even to nonvascular smooth muscle. Significant levels of sugar-phosphates (SP), phosphodiesters (PDE) were detected, as well as occasionnally a peak in the diphosphodiester region. Experiments with phosphate-free perfusate demonstrated a very low level of intracellular inorganic phosphate. As expected from previous data, free ADP levels in tonic arterial tissue were found much higher than in any other muscle. Addition of norepinephrine into the perfusate induced transient decrease in ATP and PCr levels, associated with an increased production of phosphorylated intermediates. At the early stage of renovascular hypertension, aortic energetic pattern was characterized by an increased ADP/ATP ratio. Natural abundant 13C spectra were recorded from dog aortic fragments and showed mainly resonances attributed to fatty components. After addition of a shift-reagent, dysprosium tripolyphosphate, 23Na-NMR allowed separation of intra- and extracellular Na of perfused rabbits aortas. Proton NMR of lyophilized aortic fragments revealed several peaks originating from biologically relevant molecules, lactate, creatine, taurine... These preliminary data demonstrate the feasability of multinuclear NMR spectroscopy of vascular tissue and are suggestive of the potential of the method when it will be combined with monitoring of functional parameters.
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PMID:Arterial metabolism as studied in vitro by NMR: preliminary results in normotensive and hypertensive aortas. 242 80

The purpose of this study was to correlate bleeding complications during and after treatment with recombinant tissue-type plasminogen activator (rt-PA) with serial template bleeding time measurements, with ADP-induced platelet aggregation, with clinical characteristics, and with hemostatic parameters. Fifty-two of 55 consecutive patients with acute myocardial infarction and template bleeding times (Ivy method) of less than 9.5 minutes were treated with rt-PA in a total dose of 55-212 mg (mean, 109 mg) over 90 to 360 minutes (median, 240 minutes) combined with heparin. The mean bleeding time was significantly prolonged at 90 minutes (from 5.0 +/- 1.9 to 8.2 +/- 4.3 minutes, p less than 0.0001) but returned toward baseline after 4 hours (from a median of 8.0 to 7.0 minutes, p less than 0.05). Thirteen patients (25%) suffered relatively minor but spontaneous bleeding that did not correlate with age, hypertension, smoking, partial thromboplastin time, platelet count, ADP-induced platelet aggregation, steady-state rt-PA level, or extent of fibrinogen degradation. In multivariate analysis, only the 90-minute bleeding time correlated with spontaneous bleeding (p = 0.01). Prolongation of the 90-minute bleeding time to greater than or equal to 9 minutes, which occurred in 21 patients, correlated with spontaneous bleeding with a sensitivity of 69% (95% confidence interval, 39-90%) and a specificity of 69% (95% confidence interval, 52-83%). Retrospective analysis revealed that in 14 patients taking aspirin, the bleeding time at 90 minutes was significantly more prolonged (p less than 0.05) and spontaneous bleeding significantly more frequent (p less than 0.01) than in patients not taking aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Correlation between template bleeding times and spontaneous bleeding during treatment of acute myocardial infarction with recombinant tissue-type plasminogen activator. 250 11


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