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)

The relaxation of thoracic and abdominal aortae of the spontaneously hypertensive rat (SHR) during prehypertensive (3--5 week old) and hypertensive (12--16 and 22--25 week old) stages was compared to that of matched normotensive Wistar rats (NWRs). In the thoracic aorta, the relaxation response to isoproterenol, acetylcholine, Mg2+, Mn2+, Co2+, and La3+ was less in both prehypertensive and hypertensive SHRs than in the matched NWRs; however, such difference was not evident in the abdominal aorta. Similarly, the relaxing effect of nitroglycerin and papaverine was not different in the aorta preparations of the SHR and NWR. After chronic reserpine treatment of the prehypertensive and hypertensive SHRs, the thoracic aorta still showed less relaxation in response to the aforementioned agents. Isoproterenol, but not other agents tested, produced less relaxation in the thoracic aorta from the renal hypertensive rat than from the control. Our results suggest that the decreased relaxation of the SHR thoracic aorta is not a consequence of hypertension and that the defect in the SHR thoracic aorta cannot be generalized to other vascular beds.
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PMID:Vascular relaxation in the spontaneously hypertensive rat. 616 57

To study the relative roles of sodium (Na+) and calcium ions (Ca2+) in the response of adrenal glomerulosa cells, we investigated the effects of different Na+ concentrations in the incubation media and the actions of substances that interfere with Ca2+ fluxes. Basal aldosterone secretion and response to angiotensin II (AII), adrenocorticotropic hormone (ACTH), or potassium (K+) were dependent on extracellular Na+ concentration. Veratridine, a Na+ channel opener that dissipates Na+ gradients, blocked the stimulated steroidogenic response. Mersalyl acid and tetracaine, which are potent Ca2+ antagonists, blocked the effects of aldosterone secretagogues. Divalent cations with Ca2+ antagonistic action such as manganese M(n2+), nickel (Ni2+), and cobalt (Co2+) blocked the aldosterone secretory response to AII, ACTH, and K+. Barium (Ba2+) and strontium (Sr2+), known to mimick Ca2+ effects, increased or did not affect responses of the glomerulosa cells. Sodium vanadate, an inhibitor of ATP-dependent Ca2+ translocation, did not alter the stimulated aldosterone responses. Trifluoperazine (10(-6) M), an inhibitor of calmodulin, blocked AII and K+-induced aldosterone secretion, but was partially effective on ACTH-stimulated aldosterone output only at a concentration of 10(-5) M. The actions of ouabain on aldosterone biosynthesis were similarly affected by all these drugs. Thus, both extracellular Na+ and Ca2+ appear to play a role in the steroidogenic response of isolated glomerulosa cells. The intracellular action of Ca2+ may involve a calmodulin-like protein. The effects of ACTH are only partially dependent on Ca2+ as a second intracellular messenger.
Hypertension
PMID:Relative roles of sodium and calcium ions in the steroidogenic response of isolated rate adrenal glomerulosa cells. 627 6

An enzyme immunoassay has been developed to measure human manganese-superoxide dismutase (Mn-SOD) in serum and urine. The assay can be done in less than 5 h, is highly sensitive (detecting limit, 0.1 ng of Mn-SOD) and simple. There is no interference from factors in serum or urine under assay conditions, and the method is specific for human Mn-SOD. Serum Mn-SOD concentrations were markedly increased in patients with liver diseases, but not in renal diseases. On the other hand, urinary Mn-SOD levels were elevated in a few patients with nephrotic syndrome and lung cancer, but were decreased in patients with hypertension. Furthermore, investigations were conducted on the clinical course of serum Mn-SOD levels in a case of alcoholic hepatitis, and on correlations between serum Mn-SOD and the conventional liver function tests. The localization of Mn-SOD in liver was also explored using immunofluorescent staining. The fluorescence was intense in the degenerated portions of liver tissue from a patient with drug-induced hepatitis.
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PMID:Enzyme immunoassay for manganese-superoxide dismutase in serum and urine. 676 11

The impact of chronic NG-nitro-L-arginine methyl ester (L-NAME)-induced hypertension (20 mg.kg-1.day-1 po, for 25 days) on pressure responsiveness was assessed in vessels ranging from arcuate arteries (ArcA) to juxtaglomerular afferent arterioles (JAA), using videomicroscopy and blood-perfused juxtamedullary nephron (JMN) preparations. Respective tail-cuff pressures of control and L-NAME rats were 127 +/- 2 (n = 8) and 173 +/- 4 mmHg (n = 5). Corresponding vessels of both groups had similar calibers at 60 mmHg. Increasing blood perfusion pressure to 200 mmHg constricted control ArcA and JAA by 26 +/- 4% (n = 20) and 43 +/- 5% (n = 15), respectively. Instead, a respective 3 +/- 4% (n = 15) and 21 +/- 9% (n = 6) pressure-induced dilation occurred in L-NAME vessels, and 86 +/- 2% of glomeruli expressed alpha-smooth muscle actin. Responses to acetylcholine (1 microM) but not to nitroprusside (1 mM) were impaired by L-NAME. Maximal relaxation induced by Mn2+ (10 mM) revealed equal basal tone and similar passive viscoelastic properties in control and L-NAME vessels. No vascular hypertrophy was found in L-NAME vessels. Chronic L-NAME hypertension is therefore associated with a selective loss of vascular autoregulation in JMNs, which may contribute to glomerular injury.
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PMID:Chronic L-NAME hypertension in rats and autoregulation of juxtamedullary preglomerular vessels. 765 92

We investigated the effect of pharmacological treatment with captopril, nitrendipine, and captopril plus nitrendipine on myocardial heterologous adenylyl cyclase desensitization and the underlying postreceptor defects in spontaneously hypertensive rats (SHR). In myocardial membranes from SHR, stimulation of adenylyl cyclase with guanylylimido-diphosphate (P < .001) and forskolin (P < .05) was significantly reduced, whereas no difference with forskolin was obtained in the presence of manganese chloride. Reconstitution of Gs alpha into Gs alpha-deficient S49 cyc- mouse lymphoma cells revealed no difference between SHR and control rats. In contrast, pertussis toxin labeling of Gi alpha was significantly increased in SHR. The reduction of adenylyl cyclase in SHR was abolished after pertussis toxin treatment of membranes. Treatment with captopril, nitrendipine, or both reduced Gi alpha and increased guanylylimidodiphosphate-stimulated adenylyl cyclase activity in SHR. In summary, heterologous adenylyl cyclase desensitization due to an increase of Gi alpha but in the presence of an unchanged activity of Gs alpha or the catalyst occurs in SHR. This alteration, which could contribute to the progression of contractile dysfunction by producing adrenergic subsensitivity, is sensitive to pharmacological treatment most likely because of a reduction of sympathetic activity.
Hypertension 1995 May
PMID:Treatment in hypertensive cardiac hypertrophy, II. Postreceptor events. 773 34

Hypertension, cigarette smoking, and nicotine augment the clinical significance of other risk factors associated with cardiovascular diseases by mechanisms which are poorly understood. Since altered trace element metabolism and antioxidant status have also been implicated in these diseases, the present study investigated the interaction of nicotine treatment and hypertension on tissue trace element concentrations and select indices of antioxidant status. Spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats were treated with nicotine, via a time release tablet at an average rate of 75 micrograms/h for 6 weeks. Systolic blood pressure in nicotine-treated SHRs was significantly higher at weeks 3 and 6 of treatment than in the SHR-controls. Blood pressure in WKY rats was not affected by nicotine. Plasma and liver iron concentrations in the nicotine-treated SHR were higher than the SHR-controls and the WKY groups. Nicotine treatment did not affect plasma and liver zinc and copper concentrations or liver manganese (Mn) concentrations. Plasma ceruloplasmin activity was increased by nicotine treatment in the SHRs. Liver Mn superoxide dismutase (MnSOD) activities and glutathione concentrations, and liver and heart glutathione reductase activities, were higher in both groups of SHRs than in the WKY groups. Red cell SOD activity in the nicotine-treated SHR was lower than in the SHR-controls. In summary, blood pressure increased more rapidly in the nicotine-treated SHRs compared to the controls. The marked effects on antioxidant status observed were attributable more to hypertension than to the nicotine treatment.
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PMID:Comparative effects of 6-week nicotine treatment on blood pressure and components of the antioxidant system in male spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. 774 May 54

Cardiac beta-adrenergic signal transduction was examined in chronic portal vein-stenosed rats. Basal tension and maximum rate of tension development were significantly depressed in left ventricular papillary muscles (0.21 +/- 0.03 N/cm2 and 8.2 +/- 1.7 N.s-1.cm-2, respectively) compared with sham-operated controls (0.51 +/- 0.05 N/cm2 and 19.9 +/- 4.4 N.s-1.cm-2, respectively). The positive inotropic response to isoproterenol was also attenuated. Adenosine 3',5'-cyclic monophosphate formation was decreased significantly when GTP (-41.9%), isoproterenol with GTP (-45.3%), or guanosine 5'-O-(3-thiotriphosphate) (-52.4%) was used to stimulate adenylyl cyclase, but not when Mn2+ or forskolin was used. Beta-Adrenoceptor density (sham operated 24.6 +/- 2.0 fmol/mg; portal vein stenosed 26.4 +/- 2.1 fmol/mg) and the apparent dissociation constant (sham operated 0.26 +/- 0.04 nM; portal vein stenosed 0.29 +/- 0.04 nM) were unaffected. Portal venous hypertension did not alter beta-adrenergic receptor affinity for isoproterenol. However, it was necessary for isoproterenol to occupy three times the number of receptors in papillary muscles from stenosed animals to produce an equal increase in force generation. These data suggest that although portal vein stenosis does not alter cardiac beta-adrenoceptor density or affinity for ligands, transduction of the signal between the receptor and adenylyl cyclase is adversely influenced and may be responsible for the diminished responsiveness of beta-adrenoceptors in the myocardium.
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PMID:Cardiac beta-adrenoceptor-effector coupling in portal vein-stenosed rats. 790 Aug 2

We studied the relative etiologic importance upon the development of Parkinson's disease (PD) of occupational exposure to herbicides and other compounds, ionizing radiation exposure, family history of PD and essential tremor, smoking, and history of various viral and other medical conditions. We identified patients (n = 130) with neurologist-confirmed idiopathic PD through contacts with Calgary general hospitals, long-term care facilities, neurologists, the Movement Disorder Clinic, and the Parkinson's Society of Southern Alberta, and selected two matched (by sex and age +/- 2.5 years) community controls for each case by random digit dialing. We obtained lifetime work, chemical, radiation, medical, and smoking exposure histories and family histories of PD and essential tremor by personal interviews, and analyzed the data using conditional logistic regression for matched sets. After controlling for potential confounding and interaction between the exposure variables, using multivariate statistical methods, having a family history of PD was the strongest predictor of PD risk, followed by head trauma and then occupational herbicide use. Cases and controls did not differ in their previous exposures to smoking or ionizing radiation; family history of essential tremor; work-related contact with aluminum, carbon monoxide, cyanide, manganese, mercury, or mineral oils; or history of arteriosclerosis, chicken pox, encephalitis, hypertension, hypotension, measles, mumps, rubella, or Spanish flu. These results support the hypothesis of a multifactorial etiology for PD, probably involving genetic, environmental, trauma, and possibly other factors.
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PMID:Parkinson's disease: a test of the multifactorial etiologic hypothesis. 817 May 64

Endothelial cells are subjected to shear stresses by blood flow, normal stresses by blood pressure, and stretch by vessel expansion. These forces are known to induce secretions of several vasoactive substances probably via internal calcium mobilization (R. F. Furchgott. Circ. Res. 53: 557-573, 1983; M. J. Peach, A. L. Loeb, H. A. Singer, and J. Saye. Hypertension Dallas 7, Suppl. I: I-94-I-100, 1985). Here we report that stretching cellular membranes increased intracellular Ca2+ concentration ([Ca2+]i) in human umbilical endothelial cells cultured on silicon membranes. Upon application of a stretch pulse (3-s duration), [Ca2+]i increased rapidly and decayed slowly. The following results suggest that this increase arises from Ca2+ entry through stretch-activated (SA) channels: 1) the Ca2+ response disappeared when extracellular Ca2+ was removed; 2) gadolinium (Gd3+), a blocker for cation-selective SA channels, blocked the response but nifedipine did not; and 3) externally applied Mn2+, which is known to permeate mechanosensitive channels but not Ca2+ channels, entered the intracellular space immediately after an application of mechanical stretch. The increase in [Ca2+]i was found to consist of at least two components: an initial fast component and a delayed slower component. Ryanodine inhibited the slow component. It is suggested that stretching the membrane primarily induced extracellular Ca2+ entry through SA channels followed by Ca2+ releases from intracellular Ca2+ stores.
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PMID:Involvement of stretch-activated ion channels in Ca2+ mobilization to mechanical stretch in endothelial cells. 838 48

We compared guanine nucleotide regulatory protein (G protein) levels and function in plasma membranes from resistance vessels (mesenteric arteries) isolated from spontaneously hypertensive (SHR) and normotensive Wistar rats. G protein function was deduced from studies of adenylate cyclase activity. Although the basal level of adenylate cyclase activity (+/- Mn2+ ions) was significantly greater in SHR membranes, addition of agents that function via the stimulatory G protein--i.e., NaF (10(-2) M), (-)-isoproterenol (10(-4) M), and prostaglandin E1 (10(-5) M)--resulted in a significantly lower stimulatory response in SHR membranes. Ligands that function via the inhibitory G protein--i.e., adrenaline (10(-5) M)/propranolol (10(-5) M) (this combination being equivalent to an alpha 2-receptor agonist), carbachol (10(-3) M), and serotonin (10(-5) M)--were responsible for only slight inhibitory responses in both SHR and Wistar rat membranes, which were not significantly different. Western blotting identified the presence of Gs, Gi2, and Gi3 alpha-subunits in rat vascular smooth muscle, but there were no differences in the levels of these G protein alpha-subunits found in SHR and Wistar rat plasma membranes. The levels of the beta-subunit in the two sets of membranes were also similar. In conclusion, there is a reduced response in adenylate cyclase activity to agents that function via the stimulatory G protein in SHR membranes. However, this is not a consequence of altered levels of the different G protein subunits.
Hypertension 1993 Feb
PMID:Guanine nucleotide regulatory proteins in the spontaneously hypertensive rat. 842 82


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