Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin II (Ang II) given centrally produces an increase in blood pressure and motivation to drink. The physiological mechanisms that mediate the pressor response include release of vasopressin (AVP) and activation of the sympathetic nervous system. Using 2 new Ang II receptor antagonists, we were able to investigate the role of AT1 or AT2 receptors in mediating these effects. Adult male Sprague-Dawley rats were cannulated in the lateral ventricle and 5 days later catheterized in the carotid artery for blood pressure measurements. All experiments were carried out in conscious rats. Three treatments were given intraventricularly (i.v.t.), in 2 microliters artificial cerebrospinal fluid (ACSF) at 30 min intervals: (1) 50 ng Ang II, (2) 0.7 micrograms AT1 antagonist Losartan or 7.0 micrograms AT2 antagonist PD123177, followed by 50 ng Ang II, and (3) 50 ng Ang II, to test for recovery. Blood pressure and drinking measurements were recorded. Also, blood samples for assay of AVP were drawn at 1 or 3 min post-injection in 2 separate groups of rats. We found that both Losartan and PD123177 significantly reduced release of AVP to Ang II 1 min post-injection. Losartan significantly blocked the pressor response (P less than 0.001), while PD123177 had no significant effect. Drinking was also antagonized by Losartan (P less than 0.05) and reduced (n.s.) by PD123177. The results suggest that the pressor response to Ang II (i.v.t.) is predominantly AT1 mediated, while the drinking and AVP responses may be mediated by both receptor subtypes.
 ...
PMID:The role of angiotensin, AT1 and AT2 receptors in the pressor, drinking and vasopressin responses to central angiotensin. 152 Nov 62

The central actions of angiotensin II (ANG II) include the release of vasopressin (AVP) from the supraoptic nucleus (SON) via the pituitary gland into the blood. In conscious rats, we investigated whether catecholamines in the SON are involved in this release process. It was found that i.c.v. injections of ANG II (100 ng) selectively increased the release of norepinephrine (NA) from the SON. Like the ANG II i.c.v.-induced AVP release, this effect was prevented by i.c.v. pretreatment with the ANG II AT1 receptor antagonist, losartan (5 micrograms). The alpha-1 adrenoceptor antagonist, prazosin (0.7 nmol), injected bilaterally into the SON, significantly reduced the ANG II 100-ng i.c.v.-induced AVP release. Pretreatment with the alpha-2, beta-1 and beta-2 adrenoceptor antagonists, idazoxan, atenolol and ICI 118551, respectively, had no effect. Injections of NA into the SON increased plasma AVP at doses up to 10 nmol but not at higher doses (30-100 nmol). The effects of NA were mimicked by the alpha-1 adrenoceptor agonist, methoxamine (1-5 nmol). Bilateral pretreatment of the SON with losartan (5 micrograms) markedly inhibited the i.c.v. ANG II 100 ng-induced AVP release. The increase in AVP release after ANG II injections into the SON was also inhibited by losartan pretreatment into the SON, whereas prazosin had no effect. These results demonstrate that the ANG II-induced release of AVP is initiated through periventricular ANG II AT1 receptors and involves postsynaptic alpha-1 adrenoceptor stimulation in the SON. In addition, ANG II AT1 receptors in the SON can contribute to AVP release after periventricular ANG II receptor stimulation.
 ...
PMID:Angiotensin II-induced vasopressin release is mediated through alpha-1 adrenoceptors and angiotensin II AT1 receptors in the supraoptic nucleus. 824 29

In the past decade there have been considerable advances in basic knowledge of the renin-angiotensin system (RAS). The most important new development has been the appreciation of a tissue based RAS that can be independently regulated from the renal and vascular RAS. Greater insight into the mechanism by which angiotension-II (AII) exerts its action has been achieved through the study of molecular biology and pharmacological characterization of multiple receptor subtypes. This review summarises the features and distribution of several binding subtypes that may mediate the diverse functions of AII. Of these AT1 subtype is the most well known receptor which preferentially binds AII and AIII. The AT1 receptor site appears to mediate the classic angiotensin responses concerned with the body water balance and the maintenance of blood pressure. Less is known about the AT2 sites which also bind AII and AIII and may play a role in vascular growth. Recently, an AT3 has been discovered in cultured neuroblastoma cells and an AT4 site which preferentially binds AIV. It has been implicated in memory aquisition and retrieval and in the regulation of blood flow. Another important aspect covered is the primary and secondary messengers involved during the signal transduction after the binding of AII with receptors. A stress has also been given on the regulation of density and affinity of AII receptors by various physiological parametres as they affect the responses of RAS. Autoregulation by RAS, salt intake, development and aging and some of the hormones are important variables which could affect the AII receptors. Interactions of AII with various neuroeffector transmission involved in the regulation of water-electrolyte balance and BP regulation play an important role in the maintenance of the homeostasis. AII has been suggested to increase the NAergic transmission by enhancing synthesis, release, inhibiting reuptake by the presynaptic nerve terminals as well as enhancing cell responsiveness to the transmitter. The finding of existence of AII receptors in vagal afferent nerve terminals suggests that its baroreflex inhibitory effect is mediated by inhibiting neurotransmitter release at NTS in the baroreflex arc. Moreover, AII acts on the central receptors to stimulate AVP and ACTH secretion, drinking and peripherally increase synthesis and secretion of aldosterone. Interactions of RAS with kallikrein-kinin system and prostaglandins strongly support the existence of a balance between renal depressor and pressor substances. AII is now considered a growth promotor in cardiovascular tissues and the resultant vascular hypertrophy could contribute in the maintenance of hypertension. AII also plays a role in the kidney, not only as a regulator of hemodynamics but also in the structural changes occurring in a variety of renal disorders. In addition to the more well studied functions of RAS in RVH the review also highlights the potential contribution by the RAS to other clinically relevant syndromes such as aortoarterities induced RVH, hyperaldosteronism, heavy metal induced cardiovascular effects, diabetes mellitus and thyroid dysfunction. Although the receptor subtypes involved in these pathological states have not been definitely identified, research efforts in this direction are ongoing.
 ...
PMID:Angiotensin II--receptor subtypes characterization and pathophysiological implications. 864 21

Recently, we have shown that angiotensin II-induced AT1 receptor-mediated vasopressin release can be potentiated by blockade of periventricular AT2 receptors. In the present study, we investigated whether the AT2 receptor also exerts an inhibitory effect on osmotically induced vasopressin release. In addition, we tested the effect of the muscarinic receptor antagonist, atropine, on hyperosmolar saline-induced vasopressin release. Plasma vasopressin levels were determined 90 s after intracerebroventricularly applied hyperosmolar saline (0.2, 0.3 and 0.6 M, 5 microliters) with or without intracerebroventricular pretreatment with 1 nmol of the selective AT2 receptor antagonist, PD 123177 (1-(4-amino-3-methylphenyl)methyl-5-diphenylacetyl-4,5,6,7-tetrahy dro- 1H-imidazo[4,5-c]pyridine-6-carboxylic acid-2HCl), or with 15 nmol of the muscarinic receptor antagonist, atropine. PD 123177 potentiated 0.2 M saline-induced vasopressin release (4.7 +/- 0.8 pg/ml vs. 2.2 +/- 0.3 in vehicle-pretreated controls, P < 0.05), did not affect 0.3 M saline-induced vasopressin release (4.3 +/- 0.7 pg/ml vs. 5.4 +/- 0.6 pg/ml in vehicle-pretreated controls) and reduced 0.6 M saline-induced vasopressin release (10.0 +/- 2.3 pg/ml vs. 17.9 +/- 1.8 pg/ml in vehicle-pretreated controls, P < 0.05). Pretreatment with atropine reduced 0.3 M (2.3 +/- 0.6 pg/ml vs. 5.4 +/- 0.9 pg/ml in vehicle-pretreated controls, P < 0.05) and 0.6 M saline-induced AVP release (4.0 +/- 1.5 pg/ml vs. 18.4 +/- 2.4 pg/ml in vehicle-pretreated controls, P < 0.05) but did not affect 0.2 M saline-induced vasopressin release (2.1 +/- 0.4 pg/ml vs. 3.2 +/- 0.8 pg/ml in vehicle-pretreated controls). Our results suggest that the low saline concentration-induced, AT1 receptor-mediated, vasopressin release is under inhibitory control by periventricular AT2 receptors. Following high saline concentrations, a muscarinic mechanism seems to be predominant on which AT2 receptor stimulation acts in a facilitating manner.
 ...
PMID:Effect of angiotensin AT2 and muscarinic receptor blockade on osmotically induced vasopressin release. 874 Nov 76

The unilateral microinjection of the cholinergic agonist carbachol (CCh) directly into the posterior hypothalamic nucleus (PHN) of conscious rats evokes a dose-dependent increase in mean arterial pressure (MAP). Blockade of peripheral alpha-adrenoceptors and V1-vasopressin receptors completely inhibits this response, suggesting that the increase in MAP is mediated by increases in sympathoadrenal excitation and circulating vasopressin. Combining beta-adrenoceptor blockade with alpha-adrenoceptor and V1-vasopressin receptor blockade results in the return of a pressor response. To determine if neuropeptide Y (NPY) might be responsible for this increase, the putative NPY and irreversible alpha 1-adrenoceptor antagonist benextramine was added to alpha 2- and beta-adrenoceptor and V1-vasopressin receptor blockade provided by yohimbine, propranolol, and [D(CH2)5-Tyr(Me)]AVP (AVPX), respectively. Benextramine noncompetitively inhibited the pressor response to intravenous injection of NPY and the increase in MAP evoked by CCh microinjection into adrenergic and V1-vasopressin receptor-blocked rats, whereas benextramine competitively inhibited the pressor response to angiotensin II (AII). Furthermore, the combination of losartan, the selective AT1-AII receptor antagonist that completely blocked the increase in MAP evoked by intravenous AII, and adrenergic and V1-vasopressin receptor antagonists did not attenuate the pressor response evoked by CCh microinjection into the PHN or the increase in MAP evoked by intravenous injection of NPY. These results indicate that AII was not responsible for the CCh-evoked increase in MAP in the presence of adrenergic and V1-vasopressin receptor blockade. The similarity in the antagonism of the increase in MAP evoked by intravenous NPY injection and by CCh microinjection into the PHN of adrenergic- and V1-vasopressin receptor-blocked rats suggests that NPY might be released from sympathetic neurons after activation of the sympathetic nervous system by central administration of CCh into the PHN.
 ...
PMID:Evidence of systemic neuropeptide Y release after carbachol administration into the posterior hypothalamic nucleus. 887 93

This study investigated the role of brain angiotensin (Ang II) in thirst induced by hemorrhage. Hemorrhage by blood withdrawal from the femoral artery to 33% and 44% blood volume loss produces a dose response increase in plasma Ang II. In the brainstem there was no Ang II response to hemorrhage. In the hypothalamus, Brain Ang II was maximally elevated to 33% hemorrhage. Thus, plasma Ang II and brain Ang II had an independent response to hemorrhage. To further test the role of central versus peripheral Ang II, we tested the effect of central (50 mg) and peripheral (50 mg/kg) administration of captopril or central injection of 1 mg losartan or 3 mg CGP 42112A prior to a 33% hemorrhage in unanesthetized male Sprague-Dawley rats (250 g). Drinking was measured and AVP blood samples were taken before and after hemorrhage. The results show that central (i.v.t.) administration of captopril and losartan inhibited drinking compared to controls (0.33 +/- 0.3 ml vs. 2.3 +/- 0.8 ml: P < 0.05 and 0.20 +/- 0.09 ml vs.3.05 +/- 0.81 ml; P < 0.01, respectively) while peripheral (i.p.) captopril alone increased drinking in response to hemorrhage (5.81 +/- 0.81 ml vs. 2.3 +/- 0.8 ml; P < 0.05). AVP levels were elevated at 5 and 15 min, but neither injections of losartan or CGP 42112A i.v.t. affected this response to hemorrhage. We conclude that increased hypothalamic brain Ang II after hypovolemic hemorrhage stimulates thirst and blood pressure restoration and acts through AT1 receptors. The release of AVP in hemorrhage, however, does not rely exclusively on the angiotensinergic pathway in the brain.
 ...
PMID:The role of brain angiotensin in thirst and AVP release induced by hemorrhage. 889 85

1. Male, Long Evans rats were instrumented chronically with pulsed Doppler probes and intravascular catheters to allow assessment of regional haemodynamic changes during i.v. infusion of lipopolysaccharide (LPS, 150 micrograms kg-1 h-1). 2. In the presence of the AT1-receptor antagonists, losartan (10 mg kg-1 + 10 kg-1 h-1), the initial (1-2 h) hypotensive and renal, mesenteric and hindquarters vasodilator responses to LPS were enhanced significantly. Thereafter these effects waned, but between 8-23 h after the onset of LPS infusion, a further fall in mean atrial blood pressure (MAP) and increases in renal and hindquarters flows and conductances occurred. All these changes were significantly greater than seen with losartan or LPS alone, and exceeded the sum of their effects. 3. In the presence of captopril (2 mg kg-1 + 2 mg kg-1 h-1), the initial hypotensive and renal vasodilator responses to LPS were enhanced, but less so than in the presence of losartan. However, the effects of LPS in the presence of losartan and captopril together were not different from those in the presence of losartan alone. These observations indicate that the ability of captopril to inhibit the degradation of bradykinin had no additional influence, and the differences between the effect of captopril and losartan on the initial effects of LPS were probably due to more effective suppression of the action of angiotensin II by losartan. 4. In the absence of LPS, co-infusion of losartan and the non-selective endothelin antagonist, SB 209670 (600 micrograms kg-1 + 600 micrograms kg-1 h-1), caused a substantial, progressive hypotension (-25 +/- 2 mmHg at 24 h) accompanied by increases in renal, mesenteric and hindquarters vascular conductances (31 +/- 13, 44 +/- 9 and 45 +/- 12%, respectively), indicating an involvement of angiotensin II and endothelin in the maintenance of normal cardiovascular status in conscious, Long Evans rats. 5. In the presence of losartan and SB 209670, the initial, LPS-induced fall in MAP (-42 +/- 2 mmHg) was not different from that in the presence of losartan (-39 +/- 4 mmHg), and the increases in renal, in mesenteric, and in hindquarters vascular conductances were similar in the two conditions. However, there was no recovery in MAP, and there were persistent renal, mesenteric and hindquarter vasodilatations. 6. In all experiments involving LPS, administration of the V1- receptor antagonist, d(CH2)5-O-Me-Tyr-AVP (10 micrograms kg-1), 23 h after the start of LPS infusion caused additional hypotension and mesenteric vasodilatation, particularly. This effect was most marked in animals pretreated with losartan and SB 209670. 7. The results indicate that the initial (1-2 h) depressor and dilator effects of LPS infusion in conscious Long Evans rats are opposed by the actions of angiotensins II, rather than endothelin. However, between 2-8 h after the onset of LPS infusion the involvement of endothelin develops and that of angiotensin II fades. By 24 h after the start of infusion of LPS, the pressor and vasoconstrictor actions of endothelin wane, and a role of vasopressin is apparent. At no stage is there clear evidence for an involvement of bradykinin in the haemodynamic sequelae of endotoxaemia in this model.
 ...
PMID:Temporal differences between the involvement of angiotensin II and endothelin in the cardiovascular responses to endotoxaemia in conscious rats. 898 10

We have recently characterized a novel angiotensin II/vasopressin (Ang II/AVP) dual receptor coupled to adenylate cyclase and responding with equal sensitivity to Ang II and AVP. To gain insight into putative renal physiological roles of the dual Ang II/AVP receptor, we determined its pharmacological binding properties and renal immunocytochemical distribution. The effective displacement of [3H]AVP by [1-deamino-Val14,D-Arg8]-vasopressin (DVDAVP), a specific antidiuretic AVP analogue, supports a V2-type AVP receptor characteristic of the Ang II/AVP receptor. Displacement of 125I-Ang II by losartan but not by PD 123319 defines the Ang II/AVP receptor as a novel AT1 receptor isoform coupled to adenylate cyclase, in contrast to prototype Ca(2+)-mobilizing AT1 receptors. Neither Ang II nor AVP displace each other, corroborating the predicted discrete binding domains for Ang II and AVP but presenting an enigma for the dissection of putative Ang II- and AVP-specific hierarchical roles of the dual Ang II/AVP receptor. The renal cytolocalization of the Ang II/AVP receptor to the outer medullary thick ascending limb tubules and inner medullary collecting ducts is consistent with the well-established AVP stimulation of sodium and water reabsorption in these tubules. These data suggest that the Ang II/AVP receptor might provide the molecular basis for the observed similar stimulatory effects of Ang II and AVP on renal tubular sodium and fluid reabsorption at physiological hormone concentrations.
 ...
PMID:Renal immunocytochemical distribution and pharmacological properties of the dual angiotensin II/AVP receptor. 909 83

The isolation and molecular characterization of the Ang II/AVP receptor elucidates the structure of a novel dual receptor coupled to adenylate cyclase and responding with equal sensitivity to Ang II and AVP. The cloning strategy in conjunction with site directed mutagenesis have permitted the delineation of the Ang II and AVP binding domains within the receptor polypeptide. Pharmacological characterization of the receptor defines the AngII/AVP receptor as a novel AT1/V2 type of receptor. The renal immunocytochemical distribution of the Ang II/AVP receptor to the outer medullary thick ascending limb tubules and inner medullary collecting ducts suggests a prominent role in renal tubular sodium and fluid reabsorption.
 ...
PMID:Identification of a novel dual angiotensin II/vasopressin receptor. 985 77

Systemic hypotension causes a greater degree of vasoconstriction in intestine from 3- than from 35-day-old postnatal swine. To determine the basis for this age-dependent difference, systemic hypotension (pressure reduction to approximately 50% of baseline) was induced by creating pericardial tamponade in postnatal swine instrumented to allow measurement of intestinal hemodynamics and oxygenation in vivo. Hypotension caused gut vascular resistance to increase 77 +/- 6% in 3-day-old subjects but only 18 +/- 3% in 35-day-old subjects. Prior blockade of alpha1-receptors with phentolamine, vasopressin receptors with [d(CH2)5,D-Phe2,Ile4,Ala9-NH2]AVP, or surgical denervation of the gut loop had no effect on hypotension-induced gut vasoconstriction. Losartan, which blocks angiotensin AT1 receptors, significantly attenuated hypotension-induced gut vasoconstriction in both age groups. BQ-610, which blocks endothelin ETA receptors, also limited the magnitude of vasoconstriction but only in younger subjects. This effect may have been consequent to an interaction between endothelin and angiotensin, inasmuch as a subpressor concentration of endothelin increased the contractile response to angiotensin in mesenteric artery rings. The substantial rise in 3-day-old gut vascular resistance was partly consequent to a locally mediated vasoconstriction that occurred in response to pressure and/or flow reduction during hypotension, as evidenced by the significant attenuation of this constriction when blood flow was held constant by controlled-flow perfusion to the gut loop during hypotension. Intestinal O2 uptake was compromised to a significantly greater degree in 3- than in 35-day-old subjects during hypotension. This difference was primarily due to the inability of younger intestine to increase O2 extraction in the face of reduced blood flow and may be mediated, in part, by an effect of angiotensin II on intestinal capillary perfusion.
 ...
PMID:Effects of systemic hypotension on postnatal intestinal circulation: role of angiotensin. 995 Aug 7


1 2 Next >>