Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of the present study was to determine whether Ang II releases adenosine from the perfused rat lung. Rat lungs were perfused in situ with a physiological salt solution and were loaded with [3H]adenosine. The release of 3H from the perfused rat lung in response to intra-arterial injections of Ang II and other hormones was quantitated. Studies were conducted in both normal rats and in rats that had been nephrectomized before surgery to avoid exposure of the lungs to high levels of endogenous Ang II. Bolus doses of Ang II (10(-12)-10(-7) mol) increased the efflux of 3H from the lungs. Analysis of this effluent by thin-layer chromatography indicated that most of the Ang II-induced release of 3H was [3H]adenosine. The maximal response was usually obtained with 10(-9) mol, and higher doses (10(-8) and 10(-7) mol) mobilized less [3H]adenosine, which suggested tachyphylaxis. The effect of exogenous Ang II on [3H]adenosine release was greatly enhanced when activation of the endogenous renin-angiotensin system was prevented with prior nephrectomy. Infusion of the Ang II selective antagonist, (1-Sar-8-Ile)-Ang II, blocked Ang II-induced [3H]adenosine release. Neither norepinephrine, bradykinin, nor vasopressin consistently released adenosine. We conclude that (a) Ang II can induce the release of adenosine from the perfused rat lung, (b) this effect is receptor mediated, (c) this response is somewhat selective for Ang II, and (d) exposure to high levels of exogenous or endogenous Ang II causes tachyphylaxis so that Ang II-induced adenosine release is attenuated.
J Cardiovasc Pharmacol 1990 Jul
PMID:Angiotensin II-induced [3H]adenosine release from in situ rat lung. 169 51

The antihypertensive effect of inhibitors of the angiotensin I-converting enzyme (ACE = kininase II) results from their vasodilatory and natriuretic effects as well as their effect on baroreceptor function. In addition to the inhibition of systemic and local angiotensin II formation, other local hormonal systems may also be involved in this effect at multiple target sites. Thus, potentiation of the vasodilator and natriuretic kinin system following inhibition of kininase II is thought to contribute to the persistent hypotensive effect of ACE inhibitors despite normalization of circulating ACE activity. Although increased plasma bradykinin levels cannot be detected, we found that the enhanced kinin-dependent local vascular prostacyclin production can be blunted in vitro by aprotinin, a kallikrein inhibitor. ACE inhibition may affect the atrial natriuretic peptide (ANP) system as the renin-angiotensin system and ANP appear to play antagonistic roles at the peripheral and central nervous system levels. Inhibition of kallikrein or of kininase II were both shown to modulate the natriuretic and vasorelaxant effects of ANP. In hypertensive subjects, we found that ACE inhibition with blood pressure normalization reduces basal and stimulated plasma ANP and blunts the renal sodium excretion in response to saline loading. In contrast, we did not observe effects of acute ACE inhibition in healthy sodium-depleted volunteers on plasma vasopressin under basal conditions or in response to passive tilt. Finally, we investigated the interaction of ACE inhibition with substance P, a powerful endogenous diuretic and natriuretic peptide that may have a transmitter function in the baroreceptor reflex arch.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1990
PMID:Kinin- and non-kinin-mediated interactions of converting enzyme inhibitors with vasoactive hormones. 169 69

The effects of a Ca2+ entry blocker CD-349 and an intracellular Ca2+ release inhibitor TMB-8 on renal vasoconstriction induced by angiotensin II (ANG II) and arg-vasopressin (AVP) were examined in anesthetized dogs. Intrarenal bolus injection of ANG II (3-10 ng/kg), AVP (5-20 ng/kg) or a Ca2+ entry promotor Bay K 8644 (0.1-0.4 micrograms/kg) produced a dose-dependent decrease in renal blood flow (RBF). Intrarenal infusion of CD-349 (0.03-0.3 micrograms/kg/min) suppressed the RBF responses to ANG II, AVP, and Bay K 8644. The RBF responses to ANG II and AVP were augmented slightly by intrarenal infusion of Bay K 8644 (0.3 micrograms/kg/min). Intrarenal infusion of TMB-8 (0.03-0.1 mg/kg/min) also suppressed the RBF responses to ANG II and AVP, whereas it did not affect the RBF response to Bay K 8644. These results suggest that vasoconstriction induced by ANG II or AVP is mediated both by the influx of Ca2+ through dihydropyridine-sensitive Ca2+ channels and the release of Ca2+ from TMB-8-sensitive Ca2+ pools in the in vivo dog kidney.
J Cardiovasc Pharmacol 1990 Dec
PMID:Effects of a novel Ca2+ entry blocker, CD-349, and TMB-8 on renal vasoconstriction induced by angiotensin II and vasopressin in dogs. 170 91

The vascular smooth muscle cell of the arterial media plays a predominant role in functional and structural alterations of the arterial wall in pathophysiological processes such as arterial hypertension, atheroma, or normal aging. The observed alterations are related to the three activities of the vascular smooth muscle cell, namely contractility, secretion of proteins from the extracellular matrix, and proliferation and migration. In arterial hypertension, vascular smooth muscle cells are functionally more contracted and structurally hypertrophic, and more collagen is secreted than under normal conditions. Similar structural changes are observed in the normal aging process. With respect to vascular smooth muscle cells, atheroma is characterized by their subintimal migration and proliferation, and by excessive excretion of collagen associated with other phenotypic modifications that are expressed in their regression to a myofibroblastic state. Regardless of the pathophysiological context, these phenotypic modifications of the vascular smooth muscle cell are always linked to an activation of the phosphoinositol pathways and to calcium accumulation. The activation of the phosphoinositol pathways seems to be a common feature of the different types of arterial hypertension. This activation can be associated with an increase in vasoactive peptides such as angiotensin II, vasopressin, or endothelin as in the secondary types of hypertension or directly related to an increase in vasoconstriction; or, as an exception, it can be spontaneously active in vivo and in vitro, as in the model of cultured vascular smooth muscle cells of the spontaneously hypertensive rat (SHR).(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1990
PMID:Pathophysiological role of the vascular smooth muscle cell. 170 13

Intracerebroventricular (i.c.v.) injection of choline (50-150 micrograms) increased blood pressure (SP) and decreased heart rate (HR) in freely moving rats. Intracerebroventricular pretreatment of rats with mecamylamine (50 micrograms) blocked the reduction in HR and reduced the increase in SP induced by i.c.v. choline (150 micrograms). Central muscarinic blockade with atropine (10 micrograms, i.c.v.) reduced the pressor response to i.c.v. choline (150 micrograms) by about 70%, without influencing the decrease in HR. The decrease in HR induced by i.c.v. choline was prevented by intraarterial (i.a.) treatment of atropine methylnitrate (2 mg/kg). Intracerebroventricular choline (150 micrograms) produced a fivefold increase in catecholamine concentrations in adrenal venous plasma. Bilateral adrenalectomy reduced, but did not block, choline's effect on SP. Intracerebroventricular choline (150 micrograms) showed an ability to increase and restore SP in rats subjected to spinal cord transection or pretreatment with hexamethonium (15 mg/kg, i.a.) or with phentolamine (10 mg/kg, i.a.). Intracerebroventricular choline (150 micrograms) increased plasma vasopressin (VP) levels from 2.2 +/- 0.4 to 25.6 +/- 2.5 pg/ml. Pretreatment of rats with a VP antagonist reduced the pressor response to i.c.v. choline. It is concluded that (a) the reduction in HR results from a central nicotinic receptor-mediated increase in vagal tone, (b) the increase in SP appears to be due to activation of both nicotinic and muscarinic central cholinergic receptors, and that (c) the central activation of the adrenal medulla and the increase in plasma levels of VP are involved in the pressor response to i.c.v. choline.
J Cardiovasc Pharmacol 1991 May
PMID:Effects of intracerebroventricular injected choline on cardiovascular functions and sympathoadrenal activity. 171 98

Cardiac and peripheral circulatory responses to changes in afterload with angiotensin II (AII) and vasopressin (AVP) were investigated in ganglion-blocked (hexamethonium) conscious rats. Cardiac output (CO) was measured by thermodilution. Both hormones were infused at a dose adjusted to increase mean arterial pressure 70% above baseline. AVP (11.4 +/- 2.2 ng/kg/min, n = 6) decreased CO from 43.4 +/- 2.3 to 34.1 +/- 2.9 ml/min/100 g (p less than 0.001), whereas AII (33.4 +/- 7.4 ng/kg/min, n = 7) increased CO from 38.7 +/- 2.6 to 44.9 +/- 3.4 ml/min/100 g (p less than 0.01). Heart rate did not change with the increase in afterload with either vasoconstrictor. To study whether the different effects of AII and AVP on CO may be explained by their different actions on the venous system, changes in venous tone were evaluated by measuring mean circulatory filling pressure (MCFP) and determining the pressure gradient for venous return (PGVR). AVP changed neither MCFP nor PGVR, whereas AII increased both these parameters, 20.7 +/- 2.8% (p less than 0.01) and 20.3 +/- 6.4% (p less than 0.01), respectively, above control. We also examined the effects of AII and AVP on ventricular dynamics: left ventricular systolic pressure and left ventricular dP/dtmax increased as aortic pressure was increased in a similar manner with both vasoconstrictors. However, AVP induced a greater increase in left ventricular end diastolic pressure than AII. Our results indicate that AII induces an increase in preload by its effect on venous tone, which is adequate to increase cardiac output. The decrease in cardiac output induced by increasing afterload with AVP can be explained by two mechanisms: an inadequate venous return and a failure of the left ventricle to overcome the increased afterload.
J Cardiovasc Pharmacol 1991 Jun
PMID:Cardiocirculatory responses to AII and AVP in conscious rats. 171 15

The A7r5 smooth muscle cell line, which originally was derived from fetal rat aorta, shows spontaneous calcium oscillations associated with electrical activity (frequency of 0.2-0.5 Hz). Organic calcium antagonists such as isradipine (10(-8) M) stopped the calcium oscillations whereas calcium agonists (e.g., Bay K 8644, 10(-8) M) increased the frequency and amplitude of calcium oscillations without changing the shape of the electrical spikes. The enantiomers of the dihydropyridine SDZ 202-791 known to have opposite activity with respect to L-type Ca2+ channels antagonized each other when tested for their effects on the calcium oscillations. The modulation of the activity of these cells by inorganic ions that affect Ca2+ and K+ channels was also investigated. The addition of barium chloride (10(-4) M) to the bathing solution increased the spiking rate whereas cadmium chloride (10(-6) M) abolished the spikes. The vasoconstrictor peptide vasopressin first induced a hyperpolarization associated with the cessation of spiking activity followed by a slow depolarization. The intracellular Ca2+ concentration ([Ca2+]i), measured with the calcium indicator fura-2, was increased transiently to a level about 10-fold above basal and then gained a new steady state at about twice the basal level. Vasopressin stimulated Ca2+ release from intracellular stores (via InsP3), resulting in membrane hyperpolarization through activation of Ca(2+)-activated K+ channels. The late and long-lasting [Ca2+]i elevation was due to Ca2+ influx through dihydropyridine-insensitive channels.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1991
PMID:Modulation of electrical activity and of intracellular calcium oscillations of smooth muscle cells by calcium antagonists, agonists, and vasopressin. 172 8

To analyze the action of endothelin-1 (ET-1) on intracellular Ca ion ([Ca2+]i) handling, we have measured the [Ca2+]i transients in a cultured vascular smooth muscle cell (VSMC) line, A7r5, using two-dimensional microfluorophotometry. In the presence of 1 mM extracellular Ca2+ ([Ca2+]e), ET-1 (100 nM) induced a transient increase in [Ca2+]i due to Ca2+ release from sarcoplasmic reticulum and a subsequent sustained [Ca2+]i increase, suggestive of the entry via the voltage-dependent Ca2+ channel. The transient phase was heterogenous in the VSMC population; only two-thirds of VSMCs showed the phase, whereas all cells showed the sustained phase. To elucidate the cause of heterogeneity, we measured the [Ca2+]i using VSMCs cultured under two extreme conditions. When the cell cycle was arrested at the quiescent phase in the defined serum-free medium, the transient phase was observed in most cells. In contrast, when cell growth was promoted by the above medium plus PDGF (50 ng/ml), the [Ca2+]i response was completely abolished, whereas both the voltage-dependent Ca2+ channel and vasopressin-operated Ca2+ mobilization mechanism were universally preserved, irrespective of the culture conditions. These results may imply that the ET-1-mediated Ca2+ release mechanism is closely influenced by cell growth and preferentially effective at the quiescent phase.
J Cardiovasc Pharmacol 1991
PMID:Cell growth-dependent expression of endothelin-1 provocable Ca2+ channels in cloned vascular smooth muscle cells. 172 27

Extracellular recordings were made from anteroventral third ventricle (AV3V) and supraoptic nucleus (SON) neurons of rat hypothalamus in slice preparations. ET-3 was applied at concentrations of 10(-10) to 3 x 10(-7) M. Of 119 AV3V neurons tested, 21 (18%) were excited, 8 (6%) were slightly inhibited, and 90 (76%) were unaffected. The threshold concentration to evoke responses was approximately 10(-8) M. Excitatory responses of the AV3V neurons to ET-3 remained in a Ca(2+)-free medium. Of 120 SON neurons tested, 46 were phasic (putative vasopressin neuron) and 74 were nonphasic (putative oxytocin neuron). Of 46 phasic neurons tested, 26 (56.5%) were inhibited by ET-3, 20 (43.5%) were nonresponsive, and none was excited. Of 74 nonphasic neurons tested, 14 (19%) neurons were inhibited by ET-3, 60 (81%) were nonresponsive, and none was excited. These results suggest that ET-3 has dual effects on AV3V and SON neurons and the mechanisms of the responses may be different in the AV3V and SON neurons.
J Cardiovasc Pharmacol 1991
PMID:Endothelin-3 directly affects neurons in the anteroventral third ventricle region and supraoptic nucleus of the rat hypothalamus in vitro. 172 32

The effect of endothelin-1 (ET-1) on vasoconstrictor responses of the endothelium-denuded perfused rabbit ear artery to 5-hydroxytryptamine (5-HT), histamine, and vasopressin (VP) was studied. In low concentrations with no vasoconstrictor action (0.1 and 0.3 nM), and in a concentration that increased the perfusion pressure by 70 mm Hg (1 nM), ET-1 significantly enhanced responses to the agonists studied; this enhancement was apparently mediated by an increased influx of extracellular calcium through voltage-operated channels, as it was abolished by the calcium channel antagonist nicardipine (10 nM). In contrast, higher concentrations of ET-1 (3 and 10 nM) inhibited responses to VP and 5-HT and this inhibitory effect was accentuated in the presence of nicardipine. The possible mechanism by which ET-1 exerts this inhibitory effect on vasoconstrictor responses is discussed. Because ET-1 is released from endothelial cells that are immediately adjacent to vascular smooth muscle cells, these modulatory effects of ET-1 on responses to endogenously present vasoconstrictors may play a role in vascular function.
J Cardiovasc Pharmacol 1991
PMID:Effect of endothelin-1 on responses of isolated blood vessels to vasoconstrictor agonists. 172 43


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