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

Previously we have reported an increased renal alpha 1- and beta-adrenergic receptor expression in male spontaneously hypertensive rats that occurred ontogenetically in parallel with blood pressure elevation. However, increased receptor numbers were not accompanied by enhanced stimulation of inositol phosphate and cyclic AMP formation, respectively, indicating relative desensitization. We have now quantified alpha-subunits of the G proteins Gs (Gs short and Gs long), G(i), and Gq by immunoblotting and pertussis toxin-catalyzed ADP-ribosylation in renal membranes from 3-, 6-, 8-, and 28-week-old normotensive and spontaneously hypertensive male Wistar-Kyoto rats; additionally, 28-week-old female normotensive and spontaneously hypertensive rats were studied. During ontogenesis of male normotensive rats, Gs short increased, Gs long remained unchanged, and G(i) alpha and Gq alpha decreased. In adult normotensive rats no sex differences were detected for Gs short, Gs long, and G(i) alpha. When male rats from the normotensive and spontaneously hypertensive strains were compared, all G protein alpha-subunits were similar in the prehypertensive phase (3 weeks). In established hypertension (28 weeks), Gs long and Gq alpha were reduced, whereas Gs short and G(i) alpha remained unchanged. Gs long was also reduced during the development of hypertension (6 and 8 weeks), whereas Gs short and G(i) alpha were not consistently altered in this phase. The reduction in Gs long seen in male adult hypertensive rats was not detectable in female hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1994 May
PMID:Ontogenesis of sympathetic responsiveness in spontaneously hypertensive rats. II. Renal G proteins in male and female rats. 817 76

By the mediation of receptors in the endothelium, bradykinin, histamine, and thrombin--besides platelet-derived substances such as adenosine diphosphate and triphosphate (ADP, ATP) and serotonin--play an essential physiological role in the activation of the protective metabolic process in the endothelium, which is so important to vessel dilatation. The described process is attenuated by pathologic conditions such as e.g. hyperlipidaemia and hypertension. Furthermore, in the case of experimental hypertension, the production of contractile endothelial factors, which weaken the effect of the vasodilatory endothelial factors, is likely to increase. Obviously, an efficient antihypertensive therapy prevents from this endothelial dysfunction, at least in animal experiments.
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PMID:[Receptor-mediated endothelial vascular regulation (brief report)]. 818 16

The role of endothelium-derived contracting factor or factors in modulating relaxations and contractions to adenine nucleotides was examined in aortas from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) and Wistar rats. During contractions to phenylephrine, the relaxations to ATP were impaired significantly in SHR compared with WKY aortas with endothelium. In rings treated with NG-nitro-L-arginine (to inhibit nitric oxide synthase), the endothelium significantly augmented contractions evoked by ATP; this enhancement was greater in SHR compared with WKY aortas. Indomethacin (inhibitor of cyclooxygenase) and SQ 29,458 (antagonist of thromboxane/prostaglandin endoperoxide receptors) but not dazoxiben (inhibitor of thromboxane synthase) significantly augmented the maximal relaxation in WKY rats, abolished the impairment of the relaxation in SHR, and prevented the potentiation by the endothelium of the contractions evoked by ATP. In older animals (10 to 12 months old), the endothelium-dependent concentration-relaxation curves to ATP in SHR and WKY aortas treated with indomethacin were superimposable, as were the concentration-contraction curves (with NG-nitro-L-arginine present). Endothelium-dependent concentration-relaxation and -contraction curves to ADP obtained in these preparations overlapped also. In Wistar rats, the magnitude of the endothelium-dependent relaxations to either ATP or ADP were significantly smaller compared with the other strains, and the endothelium-dependent contractions were even smaller. Results show that adenine nucleotides stimulate the production of both endothelium-derived relaxing and contracting factors. Although there is no obvious age-related alteration in the capacity of aortas to release endothelium-derived relaxing factor, aging enhances endothelium-derived contracting factor activity in WKY rats.
Hypertension 1993 Oct
PMID:Purinergic endothelium-dependent and -independent contractions in rat aorta. 840 63

Ten years ago, the term "oxidative stress" (sigma -O2) was created to define oxidative damage inflicted to the organism. This definition brings together processes involving reactive oxygen species production and action such as free radical production during univalent reduction of oxygen within mitochondria, activation of NADPH-dependent oxidase system on the membrane surface of neutrophils, flavoprotein-catalyzed redox cycling of xenobiotics and exposure to chemical and physical agents in the environment. Since the discovery of the nitric oxide biosynthetic pathway, the deleterious effects of uncontrolled nitric oxide generation are generally classified as oxidative stress. Indeed, products of the reaction of NO and superoxide lead to oxidants such as peroxinitrite, nitrogen dioxide and hydroxyl radical, which are involved in mechanisms of cell-mediated immune reactions and defence of the intracellular environment against microbiol invasion. However NO can also regulate many biological reactions and signal transduction pathways that lead to a variety of physiological responses such as blood pressure, neurotransmission, platelet aggregation, endothelin generation or smooth muscle cell proliferation. Then the uncontrolled NO production can lead to a variety of physiological and pathophysiological responses similar to a Nitric Oxide Stress: activation of guanylate cyclase and production of cGMP: overstimulation of the inducible L-arginine to L-citrulline and NO pathway by bactericidal endotoxins and cytokines has been shown to promote undesired increases in vasodilatation, which may account for hypotension in septic shock and cytokine therapy. stimulation of auto-ADP-ribosylation and modification of SH-groups of glyceraldehyde-3-phosphate dehydrogenase in a cGMP-independent mechanism: by this way, NO in excess can strongly inhibits this important glycolytic enzyme and reduce the cellular energy production. inhibition of ribonucleotide reductase: extensive inhibition of this key enzyme in DNA synthesis in the presence of large amounts of NO could lead to important antiproliferative effects; inhibition of cytochrome P450-dependent metabolism: in Kupffer cells and hepatocytes, LPS-induced overproduction of NO has been shown to inhibit cytochrome P450-dependent metabolism and to mediate the suppression of hepatic metabolism. Moreover, NO synthetized in the peripheral nervous system is known to mediate nonadrenergic noncholinergic (NANC) neurotransmission. Overstimulation of NO synthases might therefore contribute to pathophysiological states such as: gastrointestinal motility, reflux oesophagitis, asthma, adult respiratory distress syndrome (ARDS) and chronic pulmonary artery hypertension. To these NO-mediated biological functions, one could add the biological effects of NO-derivatives such as N-nitrosocompounds, which act as carcinogenic agents, or C-nitrosocompound which were recently used as "zinc-ejecting" agents to inhibit HIV-1 infectivity of human T-lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Does nitric oxide stress exist?]. 852 Oct 87

In this study the authors examine whether smoking further heightens platelet activity and reduces fibrinolysis above that already present in mild hypertension. Ten smokers and 11 non-smokers, all with mild hypertension (defined as a diastolic pressure between 90 and 110 mm Hg) were compared for their platelet activity in vitro and in vivo and for their fibrinolytic activity. Successive measurements were made with the patients lying at rest after they had assumed the erect posture for 10 min and at the end of a 5-min moderately strenuous exercise test. The threshold for platelet aggregation by ADP in vitro was significantly lower in samples taken from the smokers at rest (1.4 +/- 0.9 mumol L(-1)) than in the non-smokers (3.5 +/- 2.5 mumol L(-1)), and the difference persisted both in the upright posture and after exercise. The level of platelet release of beta-thromboglobulin was, likewise, higher in the smokers in the upright posture. Neither standing up nor physical exercise had any significant influence on either of these two indices of platelet activity. The euglobulin clot lysis time was slightly longer in the smokers than in the non-smokers in all three experimental situations, but the differences were not significant. Inhibitor of tissue plasminogen activator was not materially different in the two groups (Table 2). The results indicate that smoking adds a further element of heightened platelet activity to that inherently present in hypertension.
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PMID:Smoking further increases platelet activity in patients with mild hypertension. 868 55

In spontaneously hypertensive rats (SHR), two separate studies examined effects on systolic blood pressure (SBP) and other cardiovascular parameters of different concentrations of sucrose compared to starches, soluble fibers (guar, psyllium), and insoluble fibers (cellulose, wheat bran). In the initial study, four diets were tested. The first diet was relatively high in sucrose calories (50%) and low in protein calories (17%)--"high sucrose"; the second diet was relatively low in sucrose (11%) and high in protein (56%) calories--"low sucrose". The third and fourth diets resembled the first and second diets respectively, but cornstarch replaced sucrose--"high and low starch". Initial SBP in each group averaged approximately 168 mmHg. After 2 weeks of ingesting the special diets, SBP of the high sucrose group rose rapidly and significantly, eventually rising above 200 mmHg by the termination of examination. The other 3 groups maintained the original SBP until after the 3rd week when the low sucrose group developed a rapid and significant SBP elevation approaching 200 mmHg. SBP of high starch and low starch remained below 181 mmHg for the two months of study. Platelets obtained at the termination of the study from the sucrose groups compared to the starch groups showed increased aggregatory responses to collagen and ADP. Further, significant elevations of triglycerides and cholesterol in the high sucrose group were found. The former parameter was also significantly elevated in the low sucrose group. In the second study, adding guar and psyllium to high sucrose diets delayed sugar-induced hypertension, while cellulose and wheat bran virtually showed no effects. Serum insulin concentrations correlated positively with SBP, serum triglycerides, and glucose--not cholesterol. Accordingly, sucrose compared to starch ingestion in SHR can adversely influence SBP and various other cardiovascular risk factors. These effects can be delayed by the presence of soluble fibers, but not insoluble fibers, in the diets.
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PMID:Effects of dietary sucrose and fibers on blood pressure in hypertensive rats. 870 56

In two-kidney-one-clip (2k-1c) renovascular hypertensive rats, the blood pressure, left ventricular weight/body weight (LVW/BW) ratio and blood platelet aggregation were increased significantly. Enalapril (Ena) 6 mg . kg-1 . d-1 ig 9 wk and Taurine 30 mg . kg-1 . d-1 ig 9 wk can not only decrease the high blood pressure, LVW/BW ratio, but also the blood platelet aggregation induced by ADP or thrombin, though still different from that of the normal group. When the 2k-1c renovascular hypertensive rats were treated with both Ena and Tau, the blood pressure and blood platelet aggregation were decreased to the same as that of the normal group, and the LVW/BW ratio was also lowered markedly, though still higher than that of the normal group. These results show that both Ena and Tau can reverse the left ventricular hypertrophy, decrease the blood pressure and suppress the blood platelet aggregation in 2k-1c renovascular hypertensive rats. When treated with both drugs, the effects can be improved. It suggests that the two drugs can enhance the effects when used together, and that they may be two good agents for treatment of hypertension.
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PMID:[Effects of taurine and enalapril on blood pressure, platelet aggregation and the regression of left ventricular hypertrophy in two-kidney-one-clip renovascular hypertensive rats]. 871 13

Platelets are intimately involved in atherosclerosis, and hypertension is a known risk factor for coronary artery disease. The angiotensin-converting enzyme (ACE) inhibitors were demonstrated to reduce hypertension and attenuate atherosclerosis. Because increased platelet aggregation was shown in hypertensive patients, the effect of a new ACE inhibitor, fosinopril, on platelet aggregation was studied. Fosinopril therapy (10 mg/day for 4 weeks) in 18 male hypertensive patients showed > or = 31% reduction in ADP-induced platelet aggregation. In vitro studies showed that fosinopril had similar inhibitory effect on ADP-induced platelet aggregation. No inhibitory effect could be detected with collagen as the aggregating agent. Finally, inhibition of platelet aggregation by fosinopril was less effective in platelets derived from hypertensive patients as compared with platelets derived from normal subjects. We conclude that fosinopril possesses a significant inhibitory activity on ADP-induced platelet aggregation both in vitro and in vivo.
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PMID:Fosinopril reduces ADP-induced platelet aggregation in hypertensive patients. 872 Apr 15

To assess platelet changes in pregnant women with chronic glomerulonephritis (CGN) and essential hypertension (EH) we estimated platelet lactic dehydrogenase activity (LDH), beta-thromboglobulin and thromboxane B2 (TxB2) plasma levels and ADP-stimulated platelet aggregability. Five groups of gravidae (26-40 weeks of gestation) were studied: with EH (n = 20), with CGN and hypertension (n = 31), with CGN without hypertension (n = 29), with late toxemia (n = 11), nonpregnant CGN women (n = 10) and healthy pregnant women (n = 20). Activation of platelet function was found in gravidae with CGN and EH. Platelet disorders were especially pronounced in pregnant women with CGN and with EH, but they were less pronounced than in control group with late toxemia. We believe that hypertension is more important stimulating factor for platelet activation than renal disease. We suggest that platelet disorders in outpatients are brought about by endothelium damage caused by elevated blood pressure.
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PMID:[Thrombocytic disorders in pregnant women with chronic glomerulonephritis and hypertension]. 902 46

1. ATP-sensitive K+ channels (KATP) are activated either by decreased intracellular ATP content or ATP/ADP ratio during ischaemia. We examined the role of a cerebral KATP in arterial pressure regulation during acute cerebral ischaemia using SHR and WKY rats. Thirteen week old male SHR or WKY rats were anaesthetized with urethane, and arterial pressure and heart rate were recorded under an artificial ventilation. 2. Intracerebroventricular (i.c.v.) injections of glibenclamide, a specific inhibitor of KATP, elicited dose-dependent vasopressor responses in WKY with bilateral ligation of carotid arteries, whereas it caused smaller vasopressor responses in SHR than WKY. 3. Systemic administration of AVP V1 receptor antagonist, OPC-21268, abolished the vasopressor responses of i.c.v. injections of glibenclamide in WKY but not in SHR. 4. Intracerebroventricular injections of glibenclamide caused both the increase in plasma concentration of AVP and the decrease in pituitary AVP content in WKY with bilateral ligation of carotid arteries, whereas it elicited no significant change in plasma and pituitary concentration of AVP in SHR with bilateral ligation of carotid arteries. 5. Cerebral KATP may play a role in the protection of excess hypertension by inhibiting AVP release from the pituitary glands during acute ischaemia in WKY, but this mechanism might not work in SHR during acute cerebral ischaemia.
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PMID:Role of cerebral ATP-sensitive K+ channels in arterial pressure regulation during acute cerebral ischaemia in SHR and WKY rats. 907 49


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