Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the in vivo interaction between calcium entry blockade by nitrendipine (a dihydropyridine calcium entry blocker) and alpha adrenergic-mediated end-organ responsiveness, four series of experiments were carried out in normal Sprague-Dawley rats. In ganglion-blocked rats (hexamethonium, 10 mg/kg i.p. plus atropine, 1.0 mg/kg i.p.), nitrendipine (0.3 mg/kg) antagonized the pressor responses to angiotensin II and vasopressin as well as to norepinephrine, thus indicating the lack of specificity of its antagonism to alpha adrenergic vasoconstriction. The results of the next two series of experiments showed first that, in pithed rats, nitrendipine (0.01 to 0.3 mg/kg) in presence of prazosin shifted the norepinephrine pressor dose-response curves to the right whereas it was ineffective in yohimbine-pretreated animals. These data, suggesting a preferential alpha-2 antagonism by nitrendipine, were confirmed further by its little effect on pressor responses to methoxamine as contrasted with its marked progressive depression of the maximum response to B-HT 920 (about 80% at the highest rate of infusion). However, qualitatively similar results were obtained by the noncalcium entry blocker vasodilators, both sodium nitroprusside and hydralazine, both of which led to minor shifts to the right of the methoxamine pressor dose-response curves, whereas dose-dependently depressing the maximum pressor response to B-HT 920 (about 70 and 40%, respectively). Thus, calcium entry blockade appeared to antagonize preferentially alpha-2-mediated vasoconstriction, but this effect was common to other vasodilators devoid of calcium entry blocking properties.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcium entry blockade by nitrendipine and alpha adrenergic responsiveness in vivo: comparison with noncalcium entry blocker vasodilators in absence and presence of phenoxybenzamine pretreatment. 298 91

Recent work with isolated blood vessels has emphasized the importance of intact endothelium when the relaxation of vascular smooth muscle is induced by acetylcholine (ACh). However, the physiologic significance of this endothelial-dependent ACh response in a complete organ circulation is unclear. We questioned whether diminished ACh vasodilation would result from damage of lung vascular endothelium and whether this response could be used as an indication of endothelial injury. We therefore induced pulmonary endothelial cell injury in one rat model by repeated injections of alpha-naphthyl thiourea (ANTU) and in a second rat model by exposing rats for 52 h to 100% oxygen at a barometric pressure of 760 torr (hyperoxia). Rats injected with Tween 80, the solvent for ANTU, or exposed to ambient Denver air served as the respective control animals. The isolated lungs of these rats were perfused with a recirculating cell- and plasma-free, physiological salt solution to study the effect of ACh or NaCl infusion on pulmonary perfusion pressure and vascular responsiveness. ANTU-treated rats demonstrated an intact vasodilatory response after ACh infusion when compared with the solvent control animals. The immediate pulmonary vasodilation after ACh infusion was slightly enhanced in the hyperoxic rat lung when compared with the rats exposed to ambient air, but there was no difference between these groups in the prolonged depression of vascular responsiveness to hypoxia or angiotensin II. Thus, in both models of lung endothelial cell injury, the pulmonary vascular responses to ACh were intact.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acetylcholine-induced pulmonary vasodilation in lung vascular injury. 300 69

The effect of alpha adrenergic receptor antagonists on concentration-dependent response to angiotensins II and III was examined in the electrically stimulated isolated rabbit vas deferens. The force generated by a nonadrenergic neural mechanism was reduced by both peptides whereas the force generated by adrenergic neural mechanisms was enhanced. Angiotensin III-induced inhibition of the nonadrenergic contraction was significantly greater than that of angiotensin II for all groups. Yohimbine (1 X 10(-4) M), an alpha-2 receptor antagonist, attenuated the depression of the nonadrenergic contraction produced by angiotensins II and III. Yohimbine (1 X 10(-5) and 1 X 10(-4) M) also significantly reduced angiotensin II-induced prostaglandin E (PGE) synthesis. Yohimbine only significantly altered the angiotensin III-induced PGE synthesis at an antagonist concentration of 1 X 10(-4) M. Rauwolscine (1 X 10(-8) and 1 X 10(-7) M) attenuated angiotensin II-induced PGE production and at a higher concentration (1 X 10(-6) M) reduced angiotensin III-induced PGE production. The alpha-1 antagonist, prazosin (1 X 10(-6) M), did not alter nonadrenergic contractile or PGE responses to either angiotensin. The alpha-2 agonist, clonidine, both inhibited the nonadrenergic neural contraction and enhanced PGE synthesis. We interpret these data to indicate that angiotensins II and III may act via separate mechanisms to induce PGE synthesis in the vas deferens, with angiotensin II effects being more dependent on norepinephrine release from adrenergic nerves.
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PMID:Alpha adrenergic receptors mediate angiotensin-induced prostaglandin production in the rabbit isolated vas deferens. 302 11

Acetylcholine causes pulmonary vasodilation, but its mechanism of action is unclear. We hypothesized that acetylcholine-induced pulmonary vasodilation might be associated with prostacyclin formation. Therefore, we used isolated rat lungs perfused with a recirculating cell- and plasma-free physiological salt solution to study the effect of acetylcholine infusion on pulmonary perfusion pressure, vascular responsiveness and lung prostacyclin production. Acetylcholine (20 micrograms infused over 1 minute) caused immediate vasodilation during ongoing hypoxic vasoconstriction and prolonged depression of subsequent hypoxic and angiotensin II-induced vasoconstrictions. Both effects of acetylcholine were abolished by atropine pretreatment. The prolonged acetylcholine effect, but not the immediate response, was blocked by meclofenamate, an inhibitor of cyclooxygenase. The prolonged effect, but not the immediate response, of acetylcholine was associated with an increase in perfusate 6-keto-PGF1 alpha concentration. The acetylcholine stimulated increase in 6-keto-PGF1 alpha production was inhibited by meclofenamate and by atropine. Thus, blockade of prostacyclin production corresponded with blockade of the prolonged acetylcholine effect. In conclusion, acetylcholine caused in isolated rat lungs an immediate vasodilation and a prolonged, time-dependent depression of vascular responsiveness. Whereas both acetylcholine effects were under muscarinic receptor control, only the prolonged effect depended on the cyclooxygenase pathway and, presumably, prostacyclin synthesis.
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PMID:Acetylcholine induces vasodilation and prostacyclin synthesis in rat lungs. 308 79

With the failure of the heart as a pump, there ensues a series of neurohumoral compensations that defend organ perfusion at the expense of alterations in cardiac filling pressures and the distribution of blood flow to various regional circulations. Activation of the sympathetic nervous system and the renin-angiotensin II-aldosterone system and increases in circulating arginine vasopressin maintain arterial blood pressure by producing systemic arteriolar vasoconstriction and the renal retention of salt and water. Constriction of the efferent arterioles in the kidney by angiotensin II and norepinephrine promotes reabsorption of glomerular filtrate in the peritubular capillaries and maintains glomerular filtration in the face of declines in glomerular plasma flow and the glomerular permeability-surface area ultrafiltration coefficient. In resting, sodium-replete, conscious animals and humans, pharmacologic inhibition of renal cyclo-oxygenase by nonsteroidal anti-inflammatory drugs has little or no effect on renal hemodynamics. However, electrical or reflex stimulation of the renal nerves, intrarenal infusion of angiotensin II, or infusion of arginine vasopressin stimulates the release of vasodilator prostaglandins from the kidneys. In sodium-depleted animals or humans, and when cardiac output decreases, there is an increase in total peripheral vascular resistance but little change in renal vascular resistance. Increased renal synthesis of vasodilator prostaglandins (presumably by the blood vessels) maintains renal blood flow despite increased release of renin and norepinephrine from the kidneys. In these situations, pharmacologic inhibition of renal cyclo-oxygenase is accompanied by marked reductions in renal blood flow and glomerular filtration rate. When this occurs in patients with advanced heart failure, reversible oliguric renal failure may result. In this setting, cyclo-oxygenase inhibition may also increase arterial pressure and induce additional depression of cardiac function. Recent data indicate that blood vessels have the capacity to synthesize the sulfidopeptide leukotrienes C4, D4, and E4, which can constrict peripheral and renal blood vessels and alter vascular permeability. The vascular cell types responsible for leukotriene C4 synthesis and the potential roles of these vasoactive eicosanoids in kidney and other regional circulations are currently under study.
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PMID:Prostaglandins in congestive heart failure and the effects of nonsteroidal anti-inflammatory drugs. 309 62

Efferent activity in the phrenic nerve was recorded during induced hypotension and hypertension in anaesthetized, paralysed, artificially ventilated dogs. Changes in arterial pressure were induced with infusions of sodium nitroprusside, noradrenaline and angiotensin II, after which ventilation was adjusted to return the PaCO2 near to control values. The PaO2 was maintained above chemoreceptor threshold throughout. When a steady state was achieved quantitative measurements of phrenic nerve activity were made. In six dogs an increase in mean arterial pressure from 114 to 167 mm Hg caused a mean reduction of phrenic nerve activity of 28%. In six dogs a decrease in mean arterial pressure from 128 to 82 mm Hg caused an increase in phrenic nerve activity of 22%. This shows that the reduction in arterial pressure induced by vasodilator drugs causes a major sustained stimulus to respiration, while increase in arterial pressure causes marked respiratory depression.
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PMID:Efferent phrenic nerve activity during induced changes in arterial pressure. 309 69

We studied the effect of ethanol in vitro on the response of isolated rat aortas to phenylephrine and angiotensin II. We also examined the effect of chronic ethanol consumption on the phenylephrine response and the effect of ethanol in vitro on that response during the development of ethanol-induced hypertension. In acute experiments the depression of the phenylephrine dose-response produced by ethanol in vitro was greater than that for angiotensin II. Comparing the depression of these agonist dose-responses by ethanol to the depression by the receptor blockers, verapamil, prazosin and saralasin, suggests that ethanol may act like an alpha 1-adrenoceptor blocker. During chronic ethanol consumption two opposing changes occurred: (1) desensitization to phenylephrine during weeks 6-18 and, (2) tolerance to depression by ethanol in vitro during weeks 4-10. These opposing changes may cancel each other which suggests that the hypertension due to chronic ethanol consumption is probably not due to an action of ethanol on the vasculature.
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PMID:Effect of acute and chronic ethanol on the agonist responses of vascular smooth muscle. 320 35

Differential solute clearances and hormone assays were used to characterize the effect of a large, protein-rich meal (1.5 g/kg) on glomerular function in 12 healthy volunteers (group I) and 12 patients with chronic glomerular disease (group II). Changes from baseline during 3 h after the meal included an elevation of plasma osmolality, progressive urinary concentration, and increasingly positive fluid balance. Plasma renin activity and arginine vasopressin levels (measured in group II only) increased significantly. Nevertheless, the rate of peak postmeal renal plasma flow became elevated by 13 and 33% in groups I and II, respectively. Corresponding peak increases in postmeal glomerular filtration rate exceeded baseline by 10 and 16%. In the proteinuric subjects of group II the fractional clearances of albumin, IgG and uncharged dextrans in the radius interval 36-54 A, declined significantly after the meal. A similar depression of the fractional dextran-clearance profile was observed also in group I. Applying the fractional clearances of relatively permeant dextrans (radii less than or equal to 44 A) to a model of hindered solute transport through an isoporous membrane, we estimate that transmembrane hydraulic pressure difference increased by 12% in group I and by between 0 to 12% in group II after protein ingestion. We conclude (i) that oral protein ingestion increases glomerular ultrafiltration pressure and rate in both normal and diseased glomeruli, (ii) that this hemodynamic response may be mediated in part by the glomerulopressor hormones angiotensin II and arginine vasopressin, and (iii) that the foregoing hemodynamic changes exert no acute adverse effect on glomerular barrier size-selectivity.
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PMID:Functional response of healthy and diseased glomeruli to a large, protein-rich meal. 327 94

Previous work in this and other laboratories has demonstrated that captopril exacerbates the hypotension produced in dogs by endotoxin. This depressor effect of captopril could result from the potentiation of bradykinin (BK) or inhibited formation of angiotensin II (AII). Anesthetized adult mongrel dogs were used in the current study. In each, the right femoral vein and artery were cannulated for the administration of drugs and monitoring of arterial pressure. A tracheostomy was performed, and the animal was respired with room air. It was found that after injection of endotoxin, AII receptor blockade (Sar1, Ile8-AII) produced a mean arterial pressure (MAP) response statistically similar to that elicited by captopril in combination with endotoxin. Although these results indicate no production of BK, the possibility of BK receptor inactivation during endotoxin shock cannot be disregarded. Additional studies suggested that in the dog, injections of BK can augment the depression of MAP caused by endotoxin and that this further depression can be prolonged by captopril. On the basis of these results, it can be concluded that in the early phases of canine endotoxin shock, AII plays a significant role in the maintenance of MAP and that BK is not produced in quantities sufficient to lower MAP.
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PMID:Bradykinin does not contribute to hypotension in early canine endotoxemia. 332 4

Acetyl-glyceryl-ether-phosphoryl-choline (AGEPC) is a potent platelet activating factor which induces profound circulatory changes. AGEPC is synthesized in a variety of cell types including platelets, neutrophils, macrophages, basophils and endothelial cells. Biological responses include platelet activation, neutrophil activation, release of arachidonic acid metabolites and systemic anaphylaxis. Circulatory responses to AGEPC were evaluated in the present investigation. Intravenous administration of AGEPC (30 micrograms/kg/min) to anesthetized dogs reduced blood pressure, cardiac output, myocardial contractile force, renal blood flow and glomerular filtration. Intracoronary administration of AGEPC (0.3-3 micrograms) reduced blood pressure, coronary blood flow, and myocardial contractile force. Administration of AGEPC into the femoral vascular bed increased femoral artery blood flow. The data suggest that the circulatory response to AGEPC in the dog is complex and depends on the site of administration. The predominant response is hypotension mediated at least in part through myocardial depression. Intramuscular injection of AGEPC (10-30 micrograms/kg) to conscious spontaneously hypertensive rats (SHRs) reduced systemic blood pressure and increased heart rate. In pithed rats, AGEPC decreased pressor responses to sympathetic stimulation, angiotensin II and phenylephrine. Chronotropic responses were unchanged. Thus, antihypertensive doses of AGEPC reduced pressor responsiveness nonspecifically, but do not affect pre- or post-junctional adrenergic mechanisms. High concentrations of AGEPC (100 microM) relaxed phenylephrine contracted rabbit aortic rings. Relaxation was dependent on an intact endothelium. Lyso-GEPC produced similar actions. In light of the low potency of AGEPC and the activity of lyso-GEPC, physiological significance to endothelium dependent relaxation by AGEPC in rabbit aortic rings is unlikely. The physiological role of AGEPC in circulatory homeostasis is unclear at present. AGEPC may play a hypotensive role in some forms of experimental hypertension. In addition, AGEPC may mediate part of the circulatory derangements associated with cardiac anaphylaxis. Lastly, AGEPC may be involved in circulatory control during states of platelet and/or neutrophil activation such as myocardial ischemia and shock.
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PMID:AGEPC, a vasodilator phospholipid with profound circulatory actions. 353 24


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