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)

Estimations of soluble fibrin monomer complexes (SFMC) in plasma are a convenient index of thrombin activation. Renal venous-arterial differences in plasma SFMC concentrations were determined in 16 randomly chosen diabetic patients by sampling directly and simultaneously from the renal artery and vein according to the method of Seldinger. In all subjects, SFMC concentrations were higher in the renal vein than in the renal artery, indicating that the kidney is an important source of SFMC. Venous-arterial differences were markedly elevated in patients with severe renal and retinal microangiopathy coupled with hypertension. The hypothesis is advanced that elevated plasma SFMC levels lead to abnormal fibrin deposits in lesioned glomeruli and retinal vessels. It is postulated that plasma SFMC may be a useful parameter for the assessment of diabetic vascular complications.
 ...
PMID:Increased intraglomerular thrombin formation in diabetic microangiopathy. 277 51

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.
 ...
PMID:[Aggregation of blood platelets and their energetic status in acute arterial hypertension]. 279 3

Thrombin-induced aggregation and serotonin release were markedly enhanced in platelets from spontaneously hypertensive rats (SHR) when compared with those from normotensive Wistar-Kyoto rats (WKY). Since phosphoinositides are involved in calcium-mediated platelet responses, the metabolism of these lipids was investigated in SHR and WKY by using 32P-labeled quiescent platelets. In unstimulated cells, both the rate and extent of 32P incorporation into individual inositol-containing phospholipids and phosphatidic acid were identical in SHR and WKY. This finding suggests that the pool size and basal turnover of phosphoinositides did not differ between the two strains. In contrast, early thrombin-induced phosphoinositide metabolism, when monitored as changes in [32P]phosphatidic acid, was significantly higher in SHR than in WKY. For example, a 20-second exposure to thrombin, 0.3 U/ml, induced the formation of 1.6 times more [32P]phosphatidic acid in SHR than in WKY. These results provide evidence for a leftward shift of the dose-response and time-course curves of thrombin-induced [32P]phosphatidic acid formation in SHR. Moreover, the extent of the difference between SHR and WKY was independent of the extracellular calcium concentration. Following thrombin stimulation, [32P]phosphatidic acid formation likely reflects the initial agonist-receptor interaction; therefore, these results suggest that phospholipase C activity is enhanced in platelets of SHR and that the hypersensitivity of phospholipase C in SHR may play a role in the overall alteration of cell calcium handling and, hence, in the platelet responses of SHR.
Hypertension 1987 Nov
PMID:Hypersensitivity of phospholipase C in platelets of spontaneously hypertensive rats. 282 75

We have shown earlier that abnormal platelet aggregation in spontaneously hypertensive rats (SHR) is not caused by prostaglandins. In this study platelets from SHR and normotensive (Wistar Kyoto, WKY) rats were used to examine the role of phosphoinositides and phosphorylation of 47,000 and 20,000 Dalton proteins in abnormal platelet activation in hypertension. Thrombin (0.05 U/ml) induced a rapid decrease in (32P)-P04 labelled phosphatidylinositol-4, 5-bisphosphate (PIP2), phosphatidylinositol-4-phosphate (PIP) and phosphatidylinositol (PI) in washed rat platelets. However, significantly greater loss of PIP2 and PI was seen in SHR platelets than in WKY platelets. For example the level of PIP2 declined by 32% in SHR platelets and only by 13% in WKY platelets at five seconds of incubation with thrombin. The loss of PI was similar in SHR and WKY platelets for the first five seconds of incubation with thrombin. However, by 15 seconds SHR platelets showed a significantly greater loss (24%) in PI than in WKY platelets (8%). Thrombin induced a 14% and 18% decrease in PIP at three seconds in WKY and SHR platelets respectively. In SHR platelets PIP level returned to the baseline in five seconds and then rose to 20% above the baseline by 30 seconds. In contrast PIP level in WKY platelets slowly reached the basal value by 30 seconds. Thrombin also produced a two- to three-fold greater accumulation of (32P)-phosphatidic acid (PA) in SHR platelets than in WKY platelets. Thrombin (0.05 U/ml) induced rapid phosphorylation of 47,000 Dalton (P47) and 20,000 Dalton (P20) proteins in both WKY and SHR platelets. Thrombin induced a four-fold greater increase in phosphorylation of P47 in SHR platelets than in WKY platelets in the first five seconds. Thrombin produced significantly greater increase in phosphorylation of P20 in SHR platelets (34% and 41%) than in WKY platelets (18% and 28%) at 5 and 15 seconds. Phosphorylation of P20 was followed by dephosphorylation in both WKY and SHR platelets. Aspirin (500 microM) did not affect phosphorylation of either P47 or P20 in SHR or WKY platelets. In other experiments prostaglandin E1 (0.5 microM), which stimulates adenylate cyclase via a guanine nucleotide regulatory protein termed Gs, caused an eighteen-fold increase in cyclic AMP level in SHR platelets as compared to a six-fold increase in WKY platelets. These data lead us to suggest that increased turnover of phosphoinositides and increased phosphorylation of P47 and P20 are involved in abnormal platelet activation in SHR platelets.
 ...
PMID:Thrombin-induced abnormal platelet activation in spontaneously hypertensive rats is linked with phosphoinositides turnover and phosphorylation of 47,000 and 20,000 dalton proteins. 283 38

A large number and variety of compounds (acetylcholine, adenosine diphosphate, adenosine triphosphate, arachidonic acid, bradykinin, Ca2+ ionophores, calcitonin gene-related peptide, histamine, hydralazine, substance P, thrombin, and vasoactive intestinal polypeptide) have been shown to relax arterial smooth muscle indirectly. The endothelium in muscular arteries from several species appears to have receptors for these vasodilators. Binding of one of these compounds to its endothelial receptors results in the release (and presumably synthesis) of substance(s) that act on arterial smooth muscle to cause relaxation. The name endothelium-derived relaxing factor (EDRF) has been proposed for the substance or substances responsible for inhibition of contraction. Studies to determine additivity of endothelium-dependent relaxing agents and sensitivity of EDRF-mediated responses to a variety of inhibitors suggest that a single factor or a single common mechanism induces relaxation of vascular smooth muscle. Pharmacological studies have been equivocal with regard to the postulated involvement of phospholipases or arachidonic acid and to the suggestion that EDRF is an oxidative, non-cyclooxygenase product of arachidonate. Experiments on transfer of EDRF and reversal of endothelium-dependent relaxation consistently indicate that EDRF is quite labile. There is convincing evidence that EDRF activates smooth muscle guanylate cyclase, which results in an increase in intracellular cyclic guanosine 3',5'-monophosphate levels. The stimulation of guanylate cyclase by EDRF provides a valuable and sensitive parameter for studies with arteries as well as cells in culture. At present, the identity of EDRF and its role in cardiovascular homeostasis are unknown.
Hypertension
PMID:Endothelium-derived vascular relaxing factor. 298 29

Endothelium-dependent relaxations are reduced in hypertensive rats. High dietary potassium supplementation reduces the incidence of strokes in Dahl rats independently of blood pressure, thereby suggesting a direct protective effect of the diet. Endothelium-dependent relaxations and aortic vascular architecture were studied in Dahl salt-sensitive rats fed 8% NaCl, 0.1% NaCl, or 8% NaCl plus 3.6% potassium citrate for 8 weeks. Rats fed 8% NaCl or 8% NaCl plus 3.6% potassium citrate became hypertensive, while those fed 0.1% NaCl did not. Aortic rings with and without endothelium were suspended in organ chambers filled with physiological salt solution (37 degrees C) and aerated with 95% O2, 5% CO2. In rings contracted with norepinephrine, acetylcholine and adenosine 5'-diphosphate caused endothelium-dependent relaxations that were significantly reduced in rats fed 8% NaCl as compared with those fed 0.1% NaCl. Potassium supplementation (8% NaCl/3.6% potassium citrate) significantly enhanced relaxations to acetylcholine in salt-sensitive rats, while those to adenosine 5'-diphosphate and thrombin were either minimally affected or unchanged. Relaxations to sodium nitroprusside were similar in rats with or without potassium supplementation. Hypertension significantly increased aortic medial and intimal thickness. Dietary potassium had no significant effect on the vascular architecture. These results suggest that high potassium diet enhances endothelium-dependent relaxations in Dahl rats at least in part independently of changes in blood pressure. Thus, potassium may be important for its protective effect against stroke and renal damage in this animal model of hypertension.
Hypertension 1988 Dec
PMID:High potassium diet augments endothelium-dependent relaxations in the Dahl rat. 326 44

The effects of a dihydropyridine calcium channel antagonist, nitrendipine 20 mg orally, have been investigated in 24 women in the first trimester human pregnancy in a double-blind, placebo controlled study. The effects on systemic arterial pressure, pulse rate (PR), blood loss at termination of pregnancy (TOP), plasma renin, renin substrate and aldosterone concentrations and platelet aggregation to adenosine diphosphate 0.5 microM, adrenaline bitartrate 0.1-1.0 microM, thrombin 0.05 u ml-1 and sodium arachidonate 0.1-0.2 mM were studied. Administration of nitrendipine was associated with a statistically-significant fall in diastolic pressure (BPD) the magnitude of which was directly related to the individual peak concentrations of the drug (P less than 0.02). No significant effects were observed on systolic pressure (BPS);PR rose slightly. Baseline variability of all three parameters fell in the nitrendipine-treated group over the first 2 h but then increased significantly (BPS, P less than 0.05; BPD, P less than 0.025; PR, P less than 0.005). There was a positive association in both placebo and treated groups between the rates of change of BPD and PR (P less than 0.005 for both); nitrendipine exerted a highly significant (P less than 0.001) effect on this association compatible with its effect as a vasodilator. Blood loss consequent on TOP did not differ in the two groups (nitrendipine 104 +/- 16 ml; placebo 114 +/- 20 ml). There were no significant differences in basal or stimulated hormone concentrations in the two groups. The ex vivo platelet aggregatory response in whole blood to 0.1 mM sodium arachidonate was inhibited by nitrendipine (P less than 0.05); responsiveness to the other aggregatory agents studied was not changed. There was a wide individual variation in both time to peak concentration of nitrendipine and the size of the peak, making classical pharmacokinetic analysis impossible. The median time after ingestion to peak concentration was 105 min; the median concentration was 7.8 ng ml-1. These data suggest that, in the context of the severe vasoconstriction and platelet aggregability of pregnancy-induced hypertension, further studies of this drug in pregnancy are warranted.
 ...
PMID:Some observations on the effects of a calcium channel blocker, nitrendipine, in early human pregnancy. 330 Jul 58

The adverse effects of protamine sulfate, used to neutralize the anticoagulant action of heparin, include systemic hypotension, pulmonary artery hypertension, thrombocytopenia and leukopenia. For further evaluation of protamine's mechanism of action, a three-part investigation was performed. In part I platelet-rich plasma (PRP) was prepared from canine blood samples (n = 6) taken before and 2 minutes after injection of protamine. In part II human PRP (n = 5) was preincubated with protamine or distilled water. Adenosine diphosphate-induced aggregation of protamine-treated platelets was unchanged, but thrombin-induced aggregation was inhibited in both canine and human preparations (p less than 0.05). In part III thrombocytopenia was produced in splenectomized dogs (n = 5), using microporous filters, to 4.5-8.4% of the initial platelet count. Protamine reversal of the heparinization caused hypotension (maximally -29 mmHg 90 s after protamine), but not pulmonary arterial hypertension. Leukopenia developed before additional thrombocytopenia appeared. Protamine-platelet interaction inhibits thrombin-induced platelet aggregation. Platelets may play an important role in the pulmonary pressure rise during protamine reversal, but do not mediate the systemic hypotension.
 ...
PMID:The effect of protamine sulfate on platelet function. 338 50

This study examined the relationship between a plasma factor (or factors) that inhibits the release of thromboxane A2 from platelets and excessive salt intake in rats. The plasma factor, termed platelet inhibitory factor, was also characterized. The release of thromboxane A2 from thrombin-activated platelets was reduced in Wistar rats that were uninephrectomized and given 2% saline for a week, but not in rats with acute volume expansion. Platelet inhibitory factor was extracted from the plasma of these uninephrectomized and saline-loaded rats and partially purified using membrane sieves, reverse-phase high performance liquid chromatography (HPLC), modified straight-phase HPLC, and gel-permeation column chromatography. The molecular weight of the factor was about 4300 daltons by gel filtration method. The partially purified platelet inhibitory factor decreased the release not only of thromboxane A2, but also of prostaglandin E2 and prostaglandin D2 from thrombin-activated platelets. The factor inhibited the aggregation of human platelets induced by adenosine 5'-diphosphate (ADP), collagen, and thrombin, but not that by arachidonate. The platelet inhibitory factor reduced the activities of phospholipases A2 and C but did not affect the conversion of arachidonate to thromboxane A2. Furthermore, platelet inhibitory factor decreased prostaglandin E2 production in cultured renal cells, and platelet inhibitory factor-like activity was detected in kidney extract from the salt-loaded rats. These results suggest that platelet inhibitory factor is produced by chronic salt intake and involved in the functional alterations of the platelets and probably the kidneys, mainly through its inhibitory action on the liberation of arachidonate.
Hypertension 1987 Jun
PMID:Salt-induced plasma factor that inhibits platelet thromboxane A2 release and renal prostaglandin E2 production in rats. 347 9

We studied endothelium-dependent responses to substances released from aggregating platelets in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Rings of thoracic aorta with and without endothelium were taken from adult rats and suspended for isometric tension recording in organ chambers containing modified Krebs-Ringer bicarbonate solution. Aggregating platelets caused statistically similar contractions in rings without endothelium in both strains. In rings with endothelium from SHR the contractions were significantly more pronounced than in rings with endothelium from WKY. In contracted rings with endothelium, serotonin caused a slight relaxation at lower concentrations but contraction at higher concentrations; only contractions were seen in rings without endothelium. The higher concentrations of the monoamine caused contractions, which in the SHR but not in the WKY were larger in the presence than in the absence of endothelium. In both strains adenosine diphosphate induced concentration-dependent relaxation in rings with endothelium but not in those without it; at high concentrations of adenosine diphosphate, the relaxation responses were significantly smaller in the SHR than in the WKY. Endothelium-dependent relaxation in response to thrombin did not differ in the two strains. The increased contraction in response to aggregating platelets and serotonin and the decreased relaxation in response to adenosine diphosphate in the SHR suggest that functional changes occur in the endothelium in this model of hypertension, possibly because of the release of one or more endothelium-derived contracting factors.
Hypertension 1986 Jun
PMID:Endothelium-dependent responses to platelets and serotonin in spontaneously hypertensive rats. 348 6


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