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

Bradykinin-induced relaxation of precontracted, porcine coronary artery (PCA) rings is mediated by distinctly different endothelium-derived relaxing factors depending on the contractile agent used. Thus when contracted with KCl, bradykinin-induced relaxation of PCA rings is mediated solely by nitric oxide (NO), whereas when contracted with the thromboxane mimetic U46619, a small component of the relaxation is attributable to NO and a large component is attributable to a non-NO mechanism that is independent of cyclooxygenase activity. We hypothesized that the non-NO component was mediated by arachidonic acid (AA) or by a non-cyclooxygenase product of AA metabolism. Bradykinin-induced relaxations of PCA rings precontracted with U46619 in the presence of indomethacin (10 mumol/L) were moderately attenuated by the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 100 mumol/L), whereas when precontracted with KCl, L-NAME abolished the relaxations. AA produced endothelium-dependent relaxations of rings precontracted with U46619 that were unaffected by L-NAME, whereas AA did not relax rings precontracted with KCl. In rings precontracted with U46619, in the presence of L-NAME and indomethacin the phospholipase inhibitors quinacrine (50 mumol/L) and 4-bromophenacyl bromide (10 mumol/L) attenuated bradykinin- but not AA-induced relaxations. Inhibitors of both lipoxygenase (BW 755c [100 mumol/L] and nafazatrom [20 mumol/L]) and cytochrome P-450 (proadifen [10 mumol/L] and clotrimazole [10 mumol/L]) pathways did not eliminate bradykinin- or AA-induced relaxations, although clotrimazole partially attenuated AA-induced relaxations. These findings suggest that bradykinin-induced relaxation of PCA rings is mediated by AA through a mechanism that is not dependent on cyclooxygenase, lipoxygenase, or cytochrome P-450 pathways.
Hypertension 1994 Jun
PMID:Relaxation of porcine coronary artery to bradykinin. Role of arachidonic acid. 820 38

To evaluate the effect of chronic hyperinsulinemia on blood pressure in salt-dependent hypertension, we infused insulin (1.0 IU/d, n = 15) or saline (n = 13) for 4 weeks into deoxycorticosterone acetate-salt hypertensive rats. The insulin infusion increased plasma insulin levels to 24 +/- 2 microU/mL, which was higher than in the saline-infused rats (9 +/- 1 microU/mL) but was still within the physiological range. Blood pressure was measured by the tail-cuff method twice a week, and daily sodium intake and urinary sodium excretion were calculated for 3 weeks. At week 4, arterial pressor responsiveness to norepinephrine, angiotensin II, and hexamethonium bromide was evaluated. After 14 days of chronic infusion, the insulin group showed a higher blood pressure than the saline group (on 21st day: 178 +/- 6 versus 156 +/- 5 mm Hg, P < .05 by tail-cuff method; 171 +/- 4 versus 149 +/- 3 mm Hg, P < .05 by direct intra-arterial measurement). This blood pressure difference was eliminated after ganglionic blockade with hexamethonium bromide (86 +/- 4 mm Hg in insulin-treated and 89 +/- 4 mm Hg in saline-treated rats by direct intra-arterial measurement). Throughout the experiment, neither sodium balance nor arterial pressor responsiveness to norepinephrine or angiotensin II differed between the two groups. In conclusion, chronic hyperinsulinemia in the physiological range augments the development of hypertension in salt-dependent hypertension, and this augmentation may be mediated by sympathetic stimulation independent of salt retention.
Hypertension 1994 Jan
PMID:Chronic hyperinsulinemia augments deoxycorticosterone acetate-salt hypertension. 828 49

The migration of coronary artery medial smooth muscle cells (SMCs) into the intima is proposed to be an important process of intimal thickening in coronary atherosclerotic lesions. In the current study, we examined the possible interaction of adrenomedullin, a novel vasorelaxant peptide, and angiotensin II (Ang II) on human coronary artery SMC migration using Boyden's chamber method. Ang II stimulated SMC migration in a concentration-dependent manner between 10(6) and 10(8) mol/L. This stimulation was clearly blocked by the Ang II type 1 receptor antagonist losartan but not by the type 2 receptor antagonist PD 123319. The migration stimulatory effect of Ang II was chemotactic in nature for cultured human coronary artery SMCs but was not chemokinetic. Human adrenomedullin clearly inhibited Ang II-induced migration in a concentration-dependent manner. Human adrenomedullin stimulated cAMP formation in these cells. Inhibition by adrenomedullin of Ang II-induced SMC migration was paralleled by an increase in the cellular level of cAMP. 8-Bromo-cAMP, a cAMP analogue, and forskolin, an activator of adenylate cyclase, inhibited the Ang II-induced SMC migration. These results suggest that Ang II stimulates SMC migration via type 1 receptors in human coronary artery and adrenomedullin inhibits Ang II-induced migration at least partly through a cAMP-dependent mechanism. Taken together with the finding that adrenomedullin is synthesized in and secreted from vascular endothelial cells, this peptide may play a role as a local antimigration factor in certain pathological conditions.
Hypertension 1997 Jun
PMID:Adrenomedullin is a potent inhibitor of angiotensin II-induced migration of human coronary artery smooth muscle cells. 918 Jun 34

Talsaclidine, a novel M1-receptor selective muscarinic agonist for cholinergic substitution therapy of Alzheimer's disease, activates the sympathetic nervous system in guinea pigs and dogs at the orthosympathic ganglia and the paraganglionic adrenals. Results from guinea pigs provide indirect evidence for an additional central site of action. The present investigation in anaesthetized and vagotomized guinea pigs intended to demonstrate central activation of the sympathetic nervous system directly by comparing the blood pressure effects of intracerebroventricular and intravenous injections of small doses of talsaclidine. Increasing doses of 0.2 and 0.6 mg/kg talsaclidine were injected alternately into the third cerebral ventricle and intravenously in 6 guinea pigs before and after blockade of peripheral muscarinic receptors with 1 mg/kg ipratropium bromide i.v. In another group of 6 animals the injections were given into the cisterna cerebellomedullaris using the same protocol. In both groups central administration of talsaclidine caused dose-related hypertension while intravenous injections were hypotensive. Ipratropium bromide, a peripheral antimuscarinic drug, reversed this hypotensive action of intravenous talsaclidine into hypertension, but did not inhibit the effects of central administration. In contrast, atropine, an antimuscarinic drug which passes the blood-brain barrier, abolished the effect of 0.6 mg/kg talsaclidine injected into the cisterna cerebellomedullaris of 8 guinea pigs. The hypertensive effect of a first injection of 0.6 mg/kg talsaclidine into the cisterna cerebellomedullaris of 6 guinea pigs was approximately twice as large as that of a second given 90 min after bilateral adrenalectomy. Sham operation in another 6 animals was not inhibitory. The results demonstrate that talsaclidine, a selective muscarinic M1-receptor agonist, activates central parts of the sympathetic nervous system, including central projections of the adrenals by an action mediated by central muscarinic receptors.
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PMID:Central activation of the sympathetic nervous system including the adrenals in anaesthetized guinea pigs by the muscarinic agonist talsaclidine. 960 29

Excessive nitric oxide (NO) synthesis, by inducible NO synthase (iNOS), has been implicated in the pathogenesis of inflammatory diseases such as rheumatoid arthritis. We investigated the pathophysiological role of NO using an adjuvant-induced arthritis model. Kinetics of iNOS mRNA expression in paw and spleen showed that it was induced from an early stage of the disease. To further characterize the pathophysiological relevance of iNOS induction in spleen, the mitogenic response of spleen cells was examined. ConA-induced proliferation of spleen cells from arthritic rats was completely suppressed in comparison to normal rats. Elevation of nitrite, which could be converted from NO, was also observed in the culture supernatants. Addition of three NOS inhibitors, S-(2-aminoethyl) isothiouronium bromide (ITU), aminoguanidine (AG) and LNG-nitroarginine methyl ester (L-NAME) all reduced the nitrite level and restored the proliferative response dose-dependently. These NOS inhibitors also showed anti-arthritic effects. Daily subcutaneous administration of either ITU at 50 mg/kg or AG at 200 mg/kg suppressed the paw swelling by 50% in arthritic rats on day 18. Oral administration of L-NAME at 30 mg/kg showed a tendency to suppress the development of arthritis from day 11 to day 15. However, drug-induced hypertension was observed with L-NAME due to poor selectivity for iNOS isozyme. These results suggest that augmented NO synthesis, via iNOS induction, may be partly involved in the pathogenesis of adjuvant-induced arthritis by causing defects in lymphocyte function. Thus, selective inhibition of iNOS might be beneficial for the treatment of immunological abnormalities associated with inflammatory diseases.
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PMID:Immunological abnormality associated with the augmented nitric oxide synthesis in adjuvant-induced arthritis. 971 83

Vascular smooth muscle cell (VSMC) migration participates in atherosclerosis and arterial restenosis after balloon angioplasty. Because these processes are enhanced in insulin-resistant states, our goal was to determine whether insulin affects VSMC migration and, if so, how. The migration of primary cultured VSMCs from canine femoral artery was measured with the use of a wound migration assay and related to cGMP levels. Insulin (1 nmol/L) did not affect migration or cGMP production in control cells. When inducible nitric oxide synthase (iNOS) was induced by 24-hour preincubation with lipopolysaccharide and interleuken-1beta, basal migration decreased, cGMP production increased, and insulin inhibited migration by >90% and stimulated cGMP production by 3-fold. The nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine blocked the affect of insulin on the migration of VSMCs with iNOS. 8-Bromo-cGMP inhibited VSMC migration in control cells, and 1-H-1[1,2,4]oxadiazolo-[4, 3a]quinoxolin-1-one, a selective inhibitor of guanylate cyclase, blocked the inhibition by insulin of migration of cells with iNOS. We conclude that insulin does not normally affect cGMP production or the migration of these VSMCs. However, after the induction of iNOS, insulin stimulates cGMP production and inhibits migration via an NOS-and a cGMP-dependent mechanism.
Hypertension 2000 Jan
PMID:Insulin inhibits migration of vascular smooth muscle cells with inducible nitric oxide synthase. 1064 15

Adrenomedullin, which was discovered as a vasodilating peptide, has been reported to be produced in various organs, in which adrenomedullin regulates not only vascular tone but also cell proliferation and differentiation in an autocrine/paracrine manner. We evaluated the effect of adrenomedullin on endothelial cell apoptosis. Human umbilical vein endothelial cells underwent apoptosis when cultured in serum-free medium. Treatment with adrenomedullin reduced the number of cells with pyknotic nuclei (Hoechst 33258 staining) and inhibited cell death (dimethylthiazol-diphenyltetrazolium bromide assay) in a dose-dependent manner. The administration of adrenomedullin did not alter the expression levels of Bcl-2 family proteins. Experiments with analogs of cAMP or a cAMP-elevating agonist demonstrated that elevation of the intracellular cAMP concentration does not mediate the antiapoptotic effect of adrenomedullin. The coadministration of N-nitro-L-arginine methyl ester (2 mmol/L), an inhibitor of nitric oxide synthase, abrogated the effect of adrenomedullin. Lower doses of sodium nitroprusside (1 to 10 micromol/L), a nitric oxide donor, mimicked the antiapoptotic effect of adrenomedullin. The antiapoptotic effect of sodium nitroprusside was not attenuated by the inhibition of soluble guanylyl cyclase with 1 micromol/L oxadiazolo-quinoxalin-1-one nor could apoptosis be inhibited by the incubation of human umbilical vein endothelial cells with 1 mmol/L 8-bromo-cGMP, a cell-permeant cGMP analog. These results indicate that adrenomedullin and nitric oxide inhibit endothelial cell apoptosis via a cGMP-independent mechanism.
Hypertension 2000 Jul
PMID:Adrenomedullin and nitric oxide inhibit human endothelial cell apoptosis via a cyclic GMP-independent mechanism. 1090 17

A 63-year-old man, scheduled for a Hartmann's procedure, sustained a cervical injury with resultant complete motor and sensory loss below the fourth cervical segment 39 years prior to admission. Anesthesia was induced with propofol 70 mg, vecuronium bromide 5 mg and an endotracheal tube was placed in the trachea. Anesthesia was maintained with nitrous oxide/oxygen and fentanyl. Ventilation was controlled to maintain normocapnea. We did not employ epidual anesthesia due to inability to flex the spine. We administered fentanyl to control hypertension, but it led to hypotension. And about 500 ml of bleeding also caused hypotension. These episodes of hypotension are associated with hypovolemia and instability of vascular tone. To control hypotension, we finally selected continuous intravenous administration of norepinephrine. The manifestations of cardiovascular instability during surgery in chronic stage of cervical spinal cord injury is not only hypertension associated with autonomic hyperreflexia, but also hypotension associated with instability of vascular tone and hypovolemia.
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PMID:[A case of rectal excision in a patient with cervical spinal cord injury of chronic stage]. 1121 39

We investigated the effects of ouabain and serum from salt-loaded Dahl salt-sensitive (S) rats, which contain abundant ouabain-like compounds, on the growth and DNA synthesis of rat pheochromocytoma PC12 cells. Ouabain decreased the growth of PC12 cells, as evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, in a concentration-dependent fashion. A moderate concentration (10(-7) M) of ouabain increased DNA synthesis, as measured by 5-bromo-2'-deoxyuridine incorporation, and induced transcription of the proto-oncogenes c-myc and c-fos. Serum from salt-loaded Dahl S rats also enhanced DNA synthesis, but serum from Dahl salt-resistant rats did not. Thus ouabain-like compounds may modify the growth or differentiation of neural tissues. This effect may contribute to the development of salt-induced hypertension in Dahl S rats.
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PMID:Effects of ouabain on the growth and DNA synthesis of PC12 cells. 1124 13

In studies conducted in vitro, it has been demonstrated that estrogen has an antioxidant potential that may contribute to its protective effects on the cardiovascular system. However, the antioxidant effect of estrogen in vivo has not been demonstrated. To address this issue, in this study the effects of estrogen on oxidative stress were evaluated in microvessels studied in vivo. Oxidative stress was evaluated by using intravital microscopy in mesenteric arterioles from female spontaneously hypertensive rats (SHR) in physiological estrous (OE), ovariectomized (OVX), OVX treated with estradiol (E(2)), or estradiol + progesterone (E/P). The mesenteries were superfused with hydroethidine, a reduced and nonfluorescent precursor of ethidium bromide (EB). In the presence of reactive oxygen species, hydroethidine is transformed intracellularly in EB, which binds to DNA and can be detected by its red fluorescence. The percentage of EB-positive nuclei along the arteriolar wall in OVX (28.4 +/- 4.3) was significantly increased compared with OE (14.2 +/- 3.9; P<0.05). The OVX overproduction of oxyradicals was attenuated by E(2) (15.7 +/- 2.2) and E/P (14.8 +/- 0.8). Treatment with the superoxide dismutase mimetic MnTMPyP attenuated by 75% the oxidation of hydroethidine in both OE and OVX. Conversely, mannitol, that decomposes hydroxyl radical, and L-NAME, a nitric oxide synthase inhibitor, had no significant effects on hydroethidine oxidation. No differences on hydrogen peroxide plasma concentration were observed among the groups, suggesting that superoxide anion is the most likely oxyradical involved in the increased oxidative stress observed in OVX. The treatment of mesenteries with diphenyleneiodonium (DPI), an nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase inhibitor, but not with oxypurinol, a xanthine-oxidase inhibitor, produced a significant reduction of oxyradical generation in OVX microvessels and a slight decrease in those from OE. Chronic treatment of female SHR with losartan caused similar decreases in oxyradicals in both OE and OVX, whereas diclofenac and verapamil had no effects. Together these data suggest that estrogen reduces superoxide anion bioavailability in vivo. The antioxidant effect of estrogen, which can contribute to a less pronounced endothelial dysfunction in female SHR, may be dependent on a direct modulatory action of estrogen on NADPH activity.
Hypertension 2002 Feb
PMID:In vivo evidence for antioxidant potential of estrogen in microvessels of female spontaneously hypertensive rats. 1188 81


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