Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Micropuncture studies of single nephrons have shown that macula densa solute reabsorption via a furosemide-sensitive pathway activates nitric oxide (NO) generation via neuronal NO synthase (nNOS). This pathway is enhanced during salt loading. We investigated the hypothesis that changes in NO generation via nNOS in the macula densa contribute to changes in whole kidney NO generation and action during alterations in salt intake. Groups of rats (n = 6-10) were equilibrated to high-salt (HS) or low-salt (LS) diets and were administered a vehicle (Veh), 7-nitroindazole (7-NI; a relatively selective inhibitor of nNOS), or furosemide (F; an inhibitor of macula densa solute reabsorption) with volume replacement. Compared with LS, excretion of the NO metabolites, NO2 plus NO3 (NOX) was increased during HS (LS: 9.0 +/- 0.5 vs. HS: 15.7 +/- 0.8 micromol/24 h; P < 0.001), but this difference was prevented by 7-NI (LS: 7.4 +/- 1.3 vs. HS: 9.4 +/- 1.6 micromol/24 h; NS). During nonselective blockade of NOS with NG-nitro-L-arginine methyl ester (L-NAME), renal vascular resistance (RVR) increased more in HS than LS (HS: +160 +/- 17 vs. LS: +83 +/- 10%; P < 0.001). This difference in response to nonselective NOS inhibition was prevented by pretreatment with 7-NI (HS: +28 +/- 6 vs. LS: +34 +/- 8%; NS) or F with volume replacement (HS: +79 +/- 11 vs. LS: +62 +/- 4%; NS). In conclusion, compared with salt restriction, HS intake increases NO generation and renal action that depend on nNOS and macula densa solute reabsorption.
 ...
PMID:NO generation and action during changes in salt intake: roles of nNOS and macula densa. 960 12

The sensitivity (EC50) of the ring segment of the mesenteric artery to serotonin (4.84 +/- 0.53 x 10(-7) mol.l-1) was 17x greater than that of the aortic ring segment (5.29 +/- 0.46 x 10(-6) mol.l-1). Incubation of the ring segments in physiological salt solution (PSS) containing methylene blue greatly potentiated the sensitivity of both the aorta and mesenteric artery to serotonin. The degree of potentiation was higher in the aorta than mesenteric artery. L-NAME also increased the sensitivity of both the aorta and mesenteric artery to serotonin and there was no difference in the degree of potentiation of the responses between the aorta and the mesenteric artery. Indomethacin inhibited the contractile responses of the aorta and the mesenteric artery to serotonin. Phenoxybenzamine reduced the contractile responses of both the aorta and the mesenteric artery by the same magnitude. Captopril (10(-4) mol.l-1) significantly attenuated the responses of the mesenteric artery more than the aorta, while methysergide (10(-8) mol.l-1) completely abolished the difference in the responses (EC50 for aorta = 3.50 +/- 0.55 x 10(-5) mol.l-1 vs 5.00 +/- 0.49 x 10(-5) mol.l-1 for mesenteric artery). This study demonstrates that rat aorta and mesenteric artery respond differently to serotonin and the differential response is due to a methylene blue sensitive factor and differences in either the receptor population or sensitivity.
 ...
PMID:Rat aorta and mesenteric artery respond differently to serotonin. 965 98

The present study evaluates the effect of blood volume expansion on the gastrointestinal transit of a charcoal meal (2.5 ml of an aqueous suspension consisting of 5% charcoal and 5% gum arabic) in awake male Wistar rats (200-270 g). On the day before the experiments, the rats were anesthetized with ether, submitted to left jugular vein cannulation and fasted with water ad libitum until 2 h before the gastrointestinal transit measurement. Blood volume expansion by i.v. infusion of 1 ml/min Ringer bicarbonate in volumes of 3, 4 or 5% body weight delayed gastrointestinal transit at 10 min after test meal administration by 21.3-26.7% (P < 0.05), but no effect was observed after 1 or 2% body weight expansion. The effect of blood volume expansion (up to 5% body weight) on gastrointestinal transit lasted for at least 60 min (P < 0.05). Mean arterial pressure increased transiently and central venous pressure increased and hematocrit decreased (P < 0.05). Subdiaphragmatic vagotomy and yohimbine (3 mg/kg) prevented the delay caused by expansion on gastrointestinal transit, while atropine (0.5 mg/kg), L-NAME (2 mg/kg), hexamethonium (10 mg/kg), prazosin (1 mg/kg) or propranolol (2 mg/kg) were ineffective. These data show that blood volume expansion delays the gastrointestinal transit of a charcoal meal and that vagal and yohimbine-sensitive pathways appear to be involved in this phenomenon. The delay in gastrointestinal transit observed here, taken together with the modifications of gastrointestinal permeability to salt and water reported by others, may be part of the mechanisms involved in liquid excess management.
 ...
PMID:Acute blood volume expansion delays the gastrointestinal transit of a charcoal meal in awake rats. 969 31

Endothelins (ET) are 21-aminoacid peptides produced ubiquitously, which were discovered originally as endothelial products. These peptides may play important roles in cardiovascular physiology and pathophysiology. As the pathophysiologic roles of endothelins in cardiovascular disease become increasingly apparent, the potential therapeutic use of endothelin antagonists or endothelin converting enzyme inhibitors is recognized. The main endothelin produced by the endothelium is ET-1. Endothelin-1 is overexpressed in the vascular wall of salt-dependent models of hypertension, such as DOCA-salt hypertensive rats, DOCA-salt-treated spontaneously hypertensive rats (SHR) and Dahl salt-sensitive rats, and in stroke-prone SHR, angiotensin II-infused rats and 1-kidney 1 clip Goldblatt hypertensive rats, but not in SHR, 2-K 1C hypertensive rats or L-NAME-treated rats. The vasoconstrictor effect of ET-1 may contribute to blood pressure elevation and its growth-promoting action to vascular hypertrophy in the hypertensive models which overexpress ET-1 in blood vessels. In rats without generalized activation of the endothelin system, expression of ET-1 is often enhanced in coronary arteries, which suggests a role for ET-1 in myocardial ischemia in hypertension. In rats overexpressing ET-1, ETA/B and ETA-selective antagonists lowered blood pressure slightly, and significantly reduced vascular growth, particularly of small arteries, suggesting that ET-1 has a direct effect on growth. Protection from renal injury and from stroke has also been demonstrated in hypertensive rats treated with endothelin antagonists. In normotensive human subjects endothelin-dependent tone can be shown in the forearm. In a study of mild hypertensive patients, the ETA/B antagonist bosentan reduced blood pressure similarly to an ACE inhibitor. Moderate to severe hypertensive patients presented enhanced expression of ET-1 mRNA in the endothelium of subcutaneous resistance arteries. In blacks with familial hypertension increased plasma levels of endothelin have been found. Thus, ET-1 may play a role in some experimental hypertensive models and in human hypertension. In summary, endothelial ET-1 may be overexpressed in the more severe forms of hypertension, and in certain special populations which may respond particularly well to endothelin antagonism. Endothelin antagonists may prove to be effective disease-modifying agents if in future clinical trials they are shown clinically to blunt vascular growth and endothelial dysfunction, reduce stroke and exert the cardioprotective and renal protective effects already reported in experimental hypertension. These agents could contribute to reduce the long-term complications of hypertension, which remains to be demonstrated in humans.
 ...
PMID:Endothelin: role in hypertension. 983 May 7

1. The interaction between the cholinergic and nitrergic innervation was investigated in circular muscle strips of the pig gastric fundus. 2. In physiological salt solution containing 4 x 10(-6) M guanethidine, electrical field stimulation (EFS; 40 V, 0.5 ms, 0.5-32 Hz, 10 s at 4 min intervals) induced small transient relaxations at 0.5-4 Hz, and large frequency-dependent contractions, sometimes followed by off-relaxations, at 8-32 Hz. 3. In the presence of L-NG-nitroarginine methyl ester (L-NAME; 3 x 10(-4) M) or physostigmine (10(-6) M), relaxations were reversed into contractions and contractions were enhanced. Physostigmine added to L-NAME further enhanced contractions, while addition of L-NAME to physostigmine had no additional effect. Off-relaxations were enhanced in the presence of L-NAME and physostigmine. L-NAME and physostigmine consistently increased basal tone. 4. Tissues contracted by 5-hydroxytryptamine or by acetylcholine responded to EFS in a similar way as in basal conditions and L-NAME reversed the relaxations at the lower stimulation frequencies into contractions and enhanced the contractions at the higher stimulation frequencies. 5. Off-relaxations in the presence of L-NAME were partially reduced by alpha-chymotrypsin (10 U ml(-1)). 6. In the absence of physostigmine, the concentration-response curve to exogenous acetylcholine was not influenced by L-NAME. 7. Contractions of the same amplitude induced by EFS at 4 Hz and by exogenous acetylcholine were either decreased or enhanced to the same extent by sodium nitroprusside (SNP; 10(-5) M), depending upon the degree of relaxation by SNP. 8. These experiments suggest that endogenous nitric oxide interferes with cholinergic neurotransmission in the pig gastric fundus by functional antagonism at the postjunctional level. The interaction is independent of the degree of contraction.
 ...
PMID:Investigation of the interaction between cholinergic and nitrergic neurotransmission in the pig gastric fundus. 988 70

The endothelins (ET) are potent 21-amino-acid vasoconstrictor peptides produced in many different tissues, particularly in the endothelium of blood vessels. ET-1 is the main endothelin secreted by the endothelium, and acts in a paracrine or autocrine fashion on blood vessels by interacting with ETA or ETB receptors on smooth muscle to stimulate contraction or on ETB receptors on endothelial cells to induce the release of vasorelaxants (nitric oxide and prostacyclin). Production of ET-1 is enhanced in several experimental models of hypertension in the rat, such as sodium-sensitive forms, e.g. deoxycorticosterone acetate (DOCA)-salt hypertensive, DOCA-salt-treated spontaneously hypertensive rats (SHR) and Dahl salt-sensitive rats, as well as other models such as stroke-prone SHR, angiotensin II-infused rats and fructose-fed rats, and possibly 1-K 1C Goldblatt hypertensive rats. In contrast, SHR, 2-K 1C Goldblatt hypertensive rats and nitric oxide-deficient (L-NAME-treated) hypertensive rats do not exhibit an ET-1 component. Endothelin dependency is manifested by excessive vascular growth, particularly in small arteries, and blood pressure lowering and regression of vascular growth after treatment with endothelin antagonists. The latter may be combined ETA/ETB or selective ETA antagonists, of which several are orally active and already in clinical development. In humans, endothelin-dependent vascular tone has been shown in studies of forearm blood flow. Enhanced expression of ET-1 mRNA has been demonstrated in the endothelium of small arteries of patients with moderate to severe hypertension. In a 4-week trial the combined ETA/ETB antagonist bosentan reduced the blood pressure of essential hypertensive patients equally to enalapril. Bosentan improved hemodynamics in patients with heart failure in acute and 2-week-long studies. Endothelin antagonists also offer promise in a rapidly fatal condition, primary pulmonary hypertension. Thus, the endothelin system appears to be involved in different forms of cardiovascular disease in experimental animals and humans, and its interruption offers great promise as a new therapeutic intervention in hypertension, heart failure and other diseases.
 ...
PMID:Endothelin and endothelin antagonists in hypertension. 988 74

This study was designed to investigate the effects of chronic inhibition of NO synthesis as well as chronic angiotensin receptor blockade with losartan in the development of hypertension, on mesenteric arterial bed reactivity as well as on the development of cardiac and kidney hypertrophy in deoxycorticosterone-salt (DOCA) hypertension. Uninephrectomized rats were divided in four experimental groups all receiving saline water to drink and treated or not with losartan over a period of 9 days. Two of these groups were administered DOCA, one of which received also N(G)-nitro-L-arginine-methyl ester (L-NAME) to drink. A third group received only L-NAME, while another group received only saline. Systolic blood pressure was similarly increased in L-NAME, DOCA, DOCA-L-NAME groups. Cardiac and kidney weights were increased in DOCA but significantly reduced in DOCA-L-NAME. Losartan prevented the development of hypertension in all groups and also prevented cardiac and kidney hypertrophy in DOCA. The hyperreactivity of mesenteric arteries to phenylephrine, measured in the presence of indomethacin, was endothelium-dependent in both L-NAME groups but not in DOCA rats. Pretreatment with BQ 123 did not modify these endothelium-dependent responses in L-NAME rats. Chronic losartan prevented endothelium-dependent phenylephrine hyperreactivity only in DOCA, whereas only the removal of the endothelium attenuated the responsiveness in both L-NAME-treated groups. Vasorelaxations to acetylcholine and isoproterenol were attenuated in the three hypertensive groups and were normalized only in DOCA and L-NAME treated with losartan. In summary, in all hypertensive groups, blood pressure was normalized by losartan independently of its effects on endothelial functions. In DOCA, losartan normalized the phenylephrine hyperreactivity through an endothelial-dependent mechanism. However, in L-NAME-treated groups an endothelial-derived contracting factor, other than angiotensin II, endothelin, or vasoconstrictor prostanoids, appears to be activated. Both NO and angiotensin II seem to play a role in the early development of hypertension and organ hypertrophy in DOCA hypertension.
 ...
PMID:Role of NO and angiotensin II in the early development of endothelial functions impairment and cardiac hypertrophy in deoxycorticosterone acetate-salt hypertension. 992 5

The aim of this study was to evaluate whether vascular remodeling and neointimal thickening occur after balloon dilatation of the nonatherosclerotic rabbit carotid artery, and whether both processes are influenced by continuous perivascular delivery of L-arginine or the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). In the first experiment, histological and morphometric evaluation of arteries was performed at different time points after balloon dilatation: 10 minutes (n=7), and 1 (n=7), 2 (n=9), 3 (n=20), or 10 (n=5) weeks. Neointimal thickening progressively contributed to luminal narrowing for at least 10 weeks after angioplasty. During the first 2 weeks after dilatation, a significant decrease of the total vessel area was measured. Ten weeks after dilatation, both the neointimal and total vessel area were increased without further changing of the luminal area. In the second experiment, endothelial injured rabbits were randomly assigned to receive 2 weeks of continuous local perivascular physiological salt solution (n=6), L-arginine (n=8), or L-NAME (n=7), starting immediately after balloon dilatation (ie, local drug delivery during the first phase of the biphasic vascular remodeling process). Perivascular L-arginine delivery significantly reduced the neointimal area, despite an increased number of neointimal Ki-67-positive smooth muscle cells. Both the luminal area and total vessel area were significantly increased. Serum L-arginine levels remained unchanged. L-NAME administration had no effect on the neointimal area, nor on the luminal and total vessel area. Neointimal formation and biphasic vascular remodeling occur after experimental balloon dilatation of the nonatherosclerotic rabbit carotid artery, and can be influenced by continuous local perivascular delivery of L-arginine.
 ...
PMID:Continuous perivascular L-arginine delivery increases total vessel area and reduces neointimal thickening after experimental balloon dilatation. 1007 85

Endothelium-dependent relaxation is not fully understood in volume-dependent models of hypertension. This study investigated the relaxation mediated by endothelium-derived nitric oxide (EDNO) and hyperpolarizing factor (EDHF) in superior mesenteric arteries from reduced renal mass hypertensive rats, an experimental model for volume-dependent hypertension. Hypertension was induced in male Wistar rats by subtotal nephrectomy and salt-loading (hypertensive group). The control group comprised rats that drank tap water after subtotal nephrectomy. Relaxation of isolated superior mesenteric arterial rings was investigated at the end of the 2-week study. In high K+-precontracted arterial rings, relaxation caused by acetylcholine (ACh) was markedly reduced in the hypertensive group compared with the findings for the control group (34+/-4% vs. 54+/-5% decrease in tension). In both groups, the relaxation was abolished by N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase. In phenylephrine-precontracted arterial rings, relaxation caused by ACh was also small in the hypertensive group, while it was large in the control group (49 +/- 5% vs. 96 +/- 2%). Superfusion of L-NAME inhibited most of the relaxation caused by ACh, but the arteries still exhibited relaxation. Apamin, a blocker of Ca-dependent K+ channel, together with L-NAME further inhibited the residual relaxation. The relaxation inhibited by apamin was also reduced in the hypertensive group. We conclude that the relaxation inhibited by L-NAME was mediated by EDNO, while that inhibited by apamin was mediated by EDHF. Endothelium-independent relaxation caused by nitroprusside and diazoxide was normal in the hypertensive group. The relaxation mediated by both EDNO and EDHF was depressed in the arteries of reduced renal mass hypertensive rats as the result of an arterial endothelial abnormality.
 ...
PMID:Impaired endothelium-dependent relaxation in mesenteric arteries of reduced renal mass hypertensive rats. 1040 Jan 64

The objective of this study was to examine the renal effects of changes in intrarenal angiotensin II levels during the administration of a cyclooxygenase inhibitor, when nitric oxide synthesis is reduced. In the first group of dogs, the administration of meclofenamate and a subpressor dose of L-NAME induced an increase (P < 0.05) in arterial pressure (14 +/- 2 mm Hg), a decrease (P < 0.05) in RBF (180 +/- 13 to 111 +/- 10 mL/min) and GFR (37 +/- 3 to 24 +/- 5 mL/min), and a reduction in the renal excretory response to a sodium load. In the second group, the administration of a converting enzyme inhibitor prevented the increase in arterial pressure, the renal vasoconstriction, and the increase in the proximal but not the distal tubular sodium reabsorption induced by the inhibition of prostaglandins and nitric oxide synthesis. In the third group, it was found that a small increase in the intrarenal angiotensin II levels, which does not produce changes in renal function in control conditions, induced a significant decrease in RBF (183 +/- 14 to 71 +/- 12 mL/min) and GFR (36 +/- 3 to 13 +/- 4 mL/min) when meclofenamate was administered and nitric oxide synthesis was slightly reduced. The results of this study suggest that renal vasoconstriction and increased proximal sodium reabsorption during the reduction of nitric oxide and prostaglandin synthesis are produced by endogenous angiotensin II levels. These results also suggest that endogenous intrarenal nitric oxide and prostaglandins may serve as homeostatic mediators of angiotensin II effects when the intrarenal levels are inappropriately elevated, as occurs in salt-sensitive hypertension.
 ...
PMID:Role of angiotensin II in the renal effects induced by nitric oxide and prostaglandin synthesis inhibition. 1049 83


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