UMLS:C0406810 - FACTA Search

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Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Differences exist between the pharmacological actions of calcium channel antagonists in blood vessels from hypertensive versus normotensive animals. In this investigation, we have examined the impact of nitric oxide synthase inhibitor N(omega) nitro-L-arginine methyl ester (L-NAME) on relaxant responses produced by the calcium channel antagonists (nifedipine, diltiazem, and mibefradil) in isolated aortic rings from Dahl salt-resistant normotensive (SRN) and salt-sensitive hypertensive (SSH) rats on a 4% salt diet. Morphological examination of the aortic rings revealed significantly larger lumen area, smooth muscle wall thickness, and perimeter in vessels of SSH rats versus SRN rats. Rank order potency for the antagonists was nifedipine > mibefradil > or = diltiazem in aortic rings from SRN rats, but mibefradil was found to be the most efficacious. The rank order potency for the antagonists in aortic rings from SSH rats was nifedipine > diltiazem > mibefradil, although all three drugs showed similar efficacy. The presence of L-NAME attenuated relaxations elicited by the antagonists in aortic rings from SRN rats. Treatment of tissues with L-NAME significantly reduced maximal response and decreased pIC(50). The presence of L-NAME had no effects on concentration-response curves to nifedipine and diltiazem in aortic rings from SSH rats, but it significantly attenuated relaxant responses of mibefradil. Our current results support the view that these calcium channel antagonists produce relaxations by mechanisms that are sensitive and insensitive to L-NAME. Moreover, the component insensitive to L-NAME was lacking in tissues from SSH rats for nifedipine and diltiazem but not mibefradil.
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PMID:Effect of nitric oxide synthase inhibitor N(omega) nitro-L-arginine methyl ester on relaxant responses to calcium channel antagonists in isolated aortic rings from Dahl normotensive and hypertensive rats. 1186 14

This study examined the effects of alterations in salt-intake on blood pressure (BP) in rats chronically treated intravenously with or without the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) (8.6 mg/kg/day). The changes in mean arterial pressure (MAP), the renal cortical and medullary blood flow (CBF and MBF), and the sodium balance were determined by implanted optical fibers and laser-Doppler flow measurement techniques in the conscious rats. The results showed that high salt intake (7.4 mEq/day) elevates CBF (139% +/- 15%), but has no significant effect on MAP or MBF in control rats; in L-NAME-treated rats, high salt intake elevates MAP, produces no change in CBF, and decreases MBF (51% +/- 14%), as well as increasing the sodium balance (0.26 +/- 0.23 mEq/day to 1.29 +/- 0.47 mEq/day). The present experiments indicated that NO appears to maintain the MBF during high salt intake and to prevent the changes in MAP, and, in the absence of NO, salt-sensitive hypertension develops. Nitric oxide plays an important role in the development of salt-sensitive hypertension with the change of MBF.
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PMID:Salt-sensitive hypertension in conscious rats induced by chronic nitric oxide blockade. 1186 50

To determine the extent to which dietary sodium modulates aldosterone-induced cardiovascular damage, and to determine whether increased dietary potassium can prevent this damage, we used the Nomega-nitro-L-arginine methyl ester (L-NAME)/angiotensin II (Ang II) rat model of cardiac injury. This model is dependent on the presence of aldosterone for the occurrence of myocardial damage. Two sets of experiments were performed. In the first set, the following groups were studied: (1) 1% NaCl to drink (control group); (2) L-NAME/Ang II with water to drink (low salt group); (3) L-NAME/Ang II/1% NaCl (high salt group); (4) L-NAME/Ang II/1% NaCl/eplerenone (eplerenone group). Systolic blood pressure increased similarly in all groups compared with controls. Compared with the controls, the high salt group, but not the low salt or eplerenone groups, developed significant myocardial damage. In the second set of experiments three groups of animals were studied: (1) L-NAME/Ang II/1%NaCl (high salt group) (2) L-NAME/Ang II/1%NaCl/eplerenone (eplerenone group), and (3) L-NAME/Ang II/1%NaCl with an extra 1% KCl in food (high dietary potassium group). Eplerenone, but not dietary potassium supplementation, prevented the development of cardiac damage. Thus, mineralocorticoid receptor antagonist treatment and low sodium diet were effective in preventing cardiac damage, which suggests that a minimal level of aldosterone and a moderately high sodium diet are both required for the development of the cardiovascular damage in the L-NAME/Ang II model. The inability of potassium supplementation to reduce myocardial damage suggests that eplerenone's protective effect is not due to its potassium-sparing ability, but is rather related to some other feature of its selective aldosterone antagonism.
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PMID:Cardiac damage prevention by eplerenone: comparison with low sodium diet or potassium loading. 1188 18

Using an isolated salt-perfused rat lung model, the authors investigated whether N-methyl-D-aspartate (NMDA) (1 mM) in the pulmonary circulation effects the pulmonary vascular responses to an acute stimulus of hypoxic insult under baseline, nitric oxide synthetase (NOS)-blocked conditions (N-omega-nitro-L arginine methyl ester; L-NAME, 2 mM), and with an NMDA receptor blocker, MK-801 (0.3 microM) added. NOS activity at baseline, and in response to hypoxia, NMDA, L-NAME, and a combination of these stimuli were also assessed. NMDA did not in itself alter hypoxic pulmonary vasoconstriction (HPV), but did significantly attenuate HPV during VOS blockade. This effect of NMDA was erased by MK-801. Assessment of NOS activity showed that hypoxia alone caused a doubling of NO production within the lung. This effect was erased by the addition of L-NAME. NMDA alone caused a significant, 3-fold increase in NOS activity, which was not further affected by hypoxic chalenge. L-NAME did not depress NOS activity in the hypoxia + NMDA group. These data suggest that NMDA receptor activation results in increased NOS activity and presumably increased production of NO. The increased NOS activity induced by NMDA receptor stimulation is resistant to the blockade effect of L-NAME. The actions of NMDA receptor activation may represent a natural protective mechanism, at least within the pulmonary vasculature, in face of acute, abnormal stimuli such as hypoxia.
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PMID:Nmda alters the development of hypoxic pulmonary vasoconstriction and nitric oxide synthetase activity in the isolated perfused rat lung. 1193 77

We examined modulation by nitric oxide (NO) of sympathetic neurotransmitter release and vasoconstriction in the isolated pump-perfused rat kidney. Electrical renal nerve stimulation (RNS; 1 and 2 Hz) increased renal perfusion pressure and renal norepinephrine (NE) efflux. Nonselective NO synthase (NOS) inhibitors [N(omega)-nitro-L-arginine methyl ester (L-NAME) or N(omega)-nitro-L-arginine], but not a selective neuronal NO synthase inhibitor (7-nitroindazole sodium salt), suppressed the NE efflux response and enhanced the perfusion pressure response. Pretreatment with L-arginine prevented the effects of L-NAME on the RNS-induced responses. 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), which eliminates NO by oxidizing it to NO(2), suppressed the NE efflux response, whereas the perfusion pressure response was less susceptible to carboxy-PTIO. 8-Bromoguanosine cGMP suppressed and a guanylate cyclase inhibitor [4H-8-bromo-1,2,4-oxadiazolo(3,4-d)benz(b)(1,4)oxazin-1-one] enhanced the RNS-induced perfusion pressure response, but neither of these drugs affected the NE efflux response. These results suggest that endogenous NO facilitates the NE release through cGMP-independent mechanisms, NO metabolites formed after NO(2) rather than NO itself counteract the vasoconstriction, and neuronal NOS does not contribute to these modulatory mechanisms in the sympathetic nervous system of the rat kidney.
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PMID:Facilitatory role of NO in neural norepinephrine release in the rat kidney. 1195 87

1. The aim of the present study was to determine whether the regulation of vascular natriuretic peptide receptors (NPR) is related to the local renin-angiotensin system (RAS). 2. Male Sprague-Dawley rats were made two-kidney, one-clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertensive to activate and inhibit the RAS, respectively. Another model of hypertension was induced by treatment with an inhibitor of nitric oxide synthesis, namely NG-nitro-L-arginine methyl ester (L-NAME). 3. The mRNA expression of NPR-A, NPR-C, angiotensin- converting enzyme (ACE) and angiotensin AT1 receptors was determined in the thoracic aorta by semiquantitative reverse transcription-polymerase chain reaction. The particulate guanylyl cyclase activity stimulated by atrial natriuretic peptide (ANP) was also determined in the membrane fraction of the thoracic aorta. 4. The plasma concentrations of ANP were increased significantly in the three models of hypertension. Plasma renin activity was increased in 2K1C hypertension, decreased in DOCA-salt hypertension and not significantly altered in L-NAME hypertension. 5. The mRNA expression of NPR-A and NPR-C was decreased, whereas that of ACE and AT1 receptors was increased in 2K1C and L-NAME hypertension. The mRNA expression of NPR-A and NPR-C was increased, whereas that of ACE and AT1 receptors was decreased in DOCA-salt hypertension. 6. The particulate guanylyl cyclase activity was decreased in 2K1C and L-NAME hypertension and increased in DOCA-salt hypertension. 7. The vascular expression of NPR may be reciprocally regulated by local RAS activity.
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PMID:Altered expression of vascular natriuretic peptide receptors in experimental hypertensive rats. 1198 39

There exists functional significance for agonists stimulated phospholipase D (PLD) and exogenous PLD in different systems, but the functional importance of PLD on vessel tone is not clear. We studied the functional importance of PLD in whole animals and in isolated vessel preparation. In in vivo study, we demonstrated that intravenous injection of PLD at 10, 30, and 100 units to male Sprague-Dawley rats did not significantly alter the mean arterial blood pressure and heart rate in 30 minutes. However, in a denuded vessel preparation, PLD from 10(-3) units/ml to 10 units/ml induced vasoconstriction from 2.8 +/- 1.7 % to 30.5 +/- 1.7 % of maximal KCI contraction in calcium enriched physiological salt solution (PSS). This vasoconstrictive effects of PLD were significantly inhibited by omission of extracellular calcium from PSS or by pretreatment the vessels with nifedipine (10(-6) M). Pretreated the denuded vessels with a protein kinase C inhibitor, chelerythrine (10(-6) M), did not significantly alter the vasoconstrictive effects of PLD. These results indicate that calcium channel rather than protein kinase C activation is involved in PLD-induced vasoconstriction. In endothelium-intact vessels, application of PLD from 10(-4) units/ml to 10 units/ml induced endothelium dependent relaxation in vessels precontracted with phenylephrine (10(-6) M). This relaxation effects of PLD were inhibited by pretreatment of vessels with indomethacin (10(-5) M) or with N-nitro-L-arginine (L-NAME, 10(-4) M), suggesting prostaglandin and nitric oxide released by PLD stimulation. The biphasic effects of PLD on vessel tone are mediated by extracellular calcium and by endothelium-derived nitric oxide and prostaglandin.
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PMID:Biphasic effects of exogenous phospholipase D on vessel tone. 1200 47

Different changes in glomerular filtration rates (GFR) in deep and superficial glomeruli have been suggested to influence renal NaCl excretion and concentrating ability. Angiotensin II (AngII) has been implicated in such changes, but the experimental evidence has been conflicting, probably because of the methodological limitation of just one 'snapshot' measurement of local GFR per kidney. We have therefore studied the effect of AngII and AT(1)-receptor blockade on glomerular filtration in outer, middle and inner cortex (OC, MC and IC, respectively) in pentobarbitone-anaesthetised rats using the aprotinin (Ap) method, providing control and experimental measurements in the same kidney. Glomerular filtration rate per gram cortical tissue was measured based on 'free' glomerular filtration of Ap followed by complete tubular uptake and a 20 min sojourn in the proximal tubular cells before breakdown and incipient return to the plasma.(125)I-labelled Ap was injected I.V. to determine control Ap clearance, followed after 13 min by injection of AngII or the A1 type AngII receptor blocker losartan and 2 min thereafter by (131)I-labelled Ap to determine clearance in the experimental period. Tracer activity in frequent blood samples and in tissue samples allowed calculation of GFR in the two periods. Mean GFR control values were: 1.13 ml min(-1) in whole kidney and 1.44, 1.27 and 0.76 ml min(-1) per gram cortical tissue in OC, MC and IC, respectively. The most sensitive and comprehensive measure of altered GFR distribution is the ratio between the relative filtration change in inner versus that in outer cortex, F = (IC(E)/IC(C))/(OC(E)/OC(C)), where subscripts E and C stand for experimental and control, respectively. F values greater than 1.00 directly indicate and quantify a relatively greater increase of filtration rate in inner than in outer cortex. We found in salt-replete rats that at practically unchanged total GFR, intravenous and intra-arterial infusion of AngII increased F to 1.07 and 1.04 (P < 0.05) whereas losartan reduced F to 0.99. After pretreatment with the inhibitor of nitric oxide production L-NAME, losartan increased total GFR by 8 % and F fell to 0.95 (P < 0.05). In salt-depleted rats losartan reduced F to 0.95 (P < 0.05) at unchanged total GFR. All IC/OC changes induced by losartan were significantly different from that obtained by AngII infusions. We conclude that deep nephrons have higher postglomerular AngII tone and also higher AngII sensitivity than superficial nephrons. The better preserved GFR in deep cortex during AngII action may contribute towards maintaining the renal concentrating ability by providing NaCl for reabsorption by the ascending limb of the loop of Henle.
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PMID:Effect of exogenous and endogenous angiotensin II on intrarenal distribution of glomerular filtration rate in rats. 1206 62

We adapted telemetry and sequence analysis employed in humans to mice and measured heart rate variability and the spontaneous baroreflex sensitivity in angiotensin II type 2 (AT2) receptor-deleted (AT2 -/-) and wild-type (AT2 +/+) mice with either deoxycorticosterone acetate (DOCA)-salt hypertension or N(omega)-nitro-L-arginine methylester hydrochloride (L-NAME) hypertension. Mean arterial pressure leveled during the day at 101+/-1 mm Hg and during the night at 109+/-1 mm Hg in AT2 receptor-deleted mice, compared with 98+/-2 mm Hg (day) and 104+/-2 mm Hg (night) in wild-type mice. Mean arterial pressure increased in AT2 receptor-deleted mice with L-NAME to 114+/-1 mm Hg (day) and 121+/-1 mm Hg (night), compared with 105+/-2 mm Hg (day) and 111+/-2 mm Hg (night), respectively. DOCA-salt also increased day and night blood pressures in AT2 receptor-deleted mice to a greater degree than in wild-type mice. Heart rate variability in the time and frequency domain was not different between AT2 receptor-deleted mice and AT2 receptor-deleted mice at baseline. Systolic blood pressure variability in the low frequency band was lower in AT2 receptor-deleted mice (0.6+/-0.1 ms2 versus 3.9+/-1.3 ms2) than in wild-type mice. Baroreceptor-heart rate reflex sensitivity was significantly increased in AT2 receptor-deleted mice compared with wild-type mice (3.4+/-0.6 versus 2.1+/-0.5 ms/mm Hg). These differences remained after DOCA-salt and L-NAME treatments. We conclude that activation of the AT2 receptor impairs arterial baroreceptor reflex function, probably by a central action. These data support the existence of an inhibitory central effect of the AT2 receptor on baroreflex function.
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PMID:Heart rate variability and baroreflex function in AT2 receptor-disrupted mice. 1215 15

A high salt diet in some species results in elevated arterial blood pressure and alterations in vascular smooth muscle responses to agonists. Weanling male Sprague-Dawley rats were given either a high salt diet containing 8 % or a low salt diet of 0.4 % sodium chloride for a period of 4 weeks. At the end of the feeding period, tail systolic pressure was higher in the high salt than in low salt rats. The rats were then killed and the intestines removed. Vascular smooth muscle (VSM) responses were estimated from the changes in lumenal diameter of pressurised second order mesenteric resistance arteries. High salt diet resulted in enhanced VSM responses to noradrenaline. The vessels dilated in response both to acetylcholine and to sodium nitroprusside and the responses were similar in vessels from both high and low salt rats. However, vessels from high salt rats were resistant to the blocking of endothelium derived nitric oxide (EDNO) with L-NAME and the responses were instead abolished by blocking endothelium derived hyperpolarising factor (EDHF) with apamin and charybdotoxin. These results show that in Sprague-Dawley rats, a high salt diet enhances the vasoconstriction in response to noradrenaline. The vasodilatory responses to acetylcholine were not significantly changed. However, they appeared to be mediated mainly by EDHF rather than by EDNO as in the low salt animals.
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PMID:Change in endothelial function in mesenteric arteries of Sprague-Dawley rats fed a high salt diet. 1218 Dec 76

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