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

We examined the effects of angiotensin II (Ang II) on isolated rabbit afferent arterioles to assess the direct effect of Ang II at the resistance vessel level in the kidney. We microdissected the superficial afferent arteriole from the kidney of New Zealand White rabbits. The afferent arteriole was cannulated with a micropipette system, and the intraluminal pressure was set at 80 mmHg. Ang II did not change the lumen diameter of the afferent arterioles. After the afferent arterioles were pretreated with aspirin DL-lysine or indomethacin, Ang II (10(-7) M) caused transient vasoconstriction in the afferent arterioles. Ang II (10(-7) M) caused persistent constriction in the afferent arterioles pretreated with NG-nitro-L-arginine (10(-4) M). Physiological doses of Ang II decreased the lumen diameter of the isolated afferent arterioles pretreated with NG-nitro-L-arginine and aspirin DL-lysine. Dup753 (10(-6) M), an AT1-receptor antagonist, abolished the vasoconstrictor effects of Ang II. These findings suggest that the isolated rabbit afferent arteriole has AT1 receptors, and the vasoconstrictor response of Ang II is counteracted by vasodilatory prostaglandins and nitric oxide.
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PMID:Effects of angiotensin II on isolated rabbit afferent arterioles. 772 23

We examined the effects of NG-nitro-L-arginine (NOARG) on antidiuresis and norepinephrine (NE) overflow in anesthetized dogs, induced by renal nerve stimulation (RNS), with or without blockade of an action of endogenous angiotensin II (AII) on the AT1 receptors by losartan. RNS (2.5-5.0 Hz) caused significant reductions in renal blood flow (RBF), glomerular filtration rate (GFR), filtration fraction (FF), urine flow (UF), and urinary excretion of sodium (UNaV) and increases in the differences in renal arteriovenous NE concentrations (NEC). Intrarenal arterial (i.r.a.) infusion of NOARG (40 micrograms/kg/min) significantly decreased RBF and UF, and increased FF, but did not alter GFR. When losartan 100 micrograms/kg/min was infused simultaneously, NOARG reduced RBF, UF, and GFR but had no effect on FF. With high-frequency RNS, NOARG enhanced the RNS-induced decreases in RBF, GFR, UF, and UNaV and the increases in NEC. During losartan infusion, NOARG-induced enhancements on renal actions in response to RNS were observed in a manner qualitatively similar to that without losartan. Most likely endogenous nitric oxide (NO) plays the role of inhibitory modulator of renal noradrenergic neurotransmission. Enhancement of renal noradrenergic neurotransmission induced by NO blockade is likely to be independent of an action of endogenous AII on the AT1 receptors.
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PMID:Interaction between nitric oxide and angiotensin II on antidiuresis and norepinephrine overflow induced by stimulation of renal nerves in anesthetized dogs. 775 43

Pulmonary vasoconstrictor responses to angiotensin (ANG) IV, the 3-8 amino acid fragment of ANG II, were compared with responses to ANG I, ANG II, and ANG III and to other vasoactive peptides in the isolated blood perfused rat lung. In terms of relative activity, ANG IV was similar in potency to bradykinin and serotonin but was approximately 100-fold less potent than ANG I, ANG II, and ANG III. PD-123319, an AT2-receptor antagonist, enhanced pressor responses to the four angiotensin peptides and to bradykinin but did not significantly change the pressor response to serotonin or to ventilatory hypoxia. DuP-753, an AT1-receptor antagonist, significantly decreased pressor responses to the four angiotensin peptides and enhanced the pressor responses to bradykinin but not to serotonin. Captopril and enalaprilat increased the pressor response to ANG IV. Meclofenamate and N omega-nitro-L-arginine methyl ester shifted the dose-response curve for ANG IV to the left in a manner similar to that observed with ANG II and ANG III. These data show that ANG IV has significant vasoconstrictor activity and suggest that responses are mediated by the activation of AT1 receptors and that vasopressor responses of the angiotensin peptides may be modulated by activation of AT2 receptors. These results also suggest that responses to ANG IV are modulated by the release of vasodilator prostaglandins and nitric oxide and that AT2 receptors have little, if any, role in mediating or modulating the pressor response to ventilatory hypoxia.
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PMID:Analysis of responses to ANG IV: effects of PD-123319 and DuP-753 in the pulmonary circulation of the rat. 786 50

To determine whether an angiotensin II receptor antagonist (AT antagonist) could improve the impaired coronary circulation as well as induce regression of cardiac hypertrophy in the hypertensive heart, and to elucidate whether the nitric oxide system in the coronary artery was involved in this mechanism, the AT1 antagonist, TCV-116 (10 mg/kg), was administered orally to spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY), and coronary flow was measured in the isolated hearts. High systolic blood pressure in SHR was significantly reduced by a 2-week treatment with TCV. Left ventricular (LV) hypertrophy in SHR regressed after TCV treatment, while LV weight in WKY was not reduced. Total minimum coronary vascular resistance (MCVR) obtained with adenosine (10(-5) M) infusions in a Langendorff apparatus was significantly greater in SHR than in WKY. Increased MCVR in SHR was reduced after TCV treatment. Coronary perfusion with NG-monomethyl-L-arginine monoacetate (L-NMMA) increased coronary vascular resistance (CVR) in WKY, while it failed to increase CVR in SHR. TCV treatment restored the responses to L-NMMA in SHR. These findings suggest that the AT1 antagonist, TCV-116, lowered the high blood pressure in SHR, concomitantly improving the impaired coronary circulation, and that it induced regression of the cardiac hypertrophy. The suppressed nitric oxide (NO) system in the coronary vessels in SHR appeared to be activated by TCV treatment.
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PMID:Effect of an angiotensin II receptor antagonist, TCV-116, on cardiac hypertrophy and coronary circulation in spontaneously hypertensive rats. 788 11

1. Regional haemodynamic responses to the homologous peptides, pituitary adenylate cyclase-activating peptide (1-27) (PACAP27) and vasoactive intestinal polypeptide (VIP) were assessed by giving 20 min infusions (1.5-15 nmol kg-1 h-1) in conscious, chronically-instrumented, Long Evans rats. 2. PACAP27 caused dose-dependent depressor and tachycardic effects associated with renal, mesenteric and hindquarters vasodilatations, although only in the latter vascular bed was there a sustained increase in flow. 3. VIP caused dose-dependent depressor and tachycardic effects that were not significantly different from those caused by equimolar doses of PACAP27. However, the hindquarters vasodilator effects of VIP (at 7.5 and 15 nmol kg-1 h-1) were greater than those of PACAP27 (at the same doses), and accompanied by reductions in renal and mesenteric flows and conductances. 4. In the presence of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 11 mumol kg-1 h-1), there was significant inhibition of the hindquarters vasodilator effects of PACAP27 and VIP (at 7.5 and 15 nmol kg-1 h-1). Under these circumstances the renal and mesenteric vasoconstrictor effects of VIP were abolished. 5. The beta 2-adrenoceptor antagonist, ICI 118551 (670 nmol kg-1 bolus, 335 nmol kg-1 h-1 infusion), reduced the matched hindquarters vasodilator responses to PACAP27 (15 nmol kg-1 h-1) and VIP (7.5 nmol kg-1 h-1), and also abolished the renal vasoconstrictor effects of VIP. 6. The AT1-receptor antagonist, losartan potassium (20 mumol kg-1), had no significant effect on the haemodynamic response to PACAP27 (15 nmol kg-1 h-1), but augmented the hypotensive action of VIP (7.5 nmol kg-1 h-1). This influence of losartan was associated with conversion of the renal and mesenteric vasoconstrictor effect of VIP to vasodilatation. 7. Our findings show that similar changes in mean systemic arterial blood pressure in response to PACAP27 and VIP conceal substantial differences in their regional haemodynamic actions. Although the hindquarters vasodilator effects of both peptides involve NO- and Beta2-adrenoceptor-mediated mechanisms,it appears that activation of the renin-angiotensin system contributes significantly to the haemodynamic effects of VIP, but not to those of PACAP27.
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PMID:Regional haemodynamic responses to pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal polypeptide in conscious rats. 791 21

The angiotensin I (AI) metabolite, A(1-7), elicited a concentration-dependent dilator response (ED50 > or = 2 microM) in porcine coronary artery rings which was markedly attenuated by the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine, and abolished after removal of the endothelium. This effect of the heptapeptide was not mimicked by AII, AIII or A(3-8) at comparable concentrations. The A(1-7)-induced relaxation was not affected by AT1 or AT2 receptor blockade or cyclo-oxygenase inhibition, but was attenuated by the B2 receptor antagonist, Hoe 140, and augmented by the angiotensin-converting enzyme (ACE) inhibitor, quinaprilat. These findings suggest that the relaxation to A(1-7) was mediated by the release of NO from the coronary endothelium through activation of an, as yet unidentified, AT receptor, the occupation of which also seems to stimulate the release of vasoactive kinins. Since A(1-7) accumulates during ACE inhibition, this mechanism may contribute to the coronary dilator effect of ACE inhibitors in vivo.
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PMID:Release of nitric oxide by angiotensin-(1-7) from porcine coronary endothelium: implications for a novel angiotensin receptor. 801 44

Renal vasoconstrictor responses to the adenosine A1 agonist N6-cyclopentyladenosine (CPA) were compared in the in situ autoperfused rat kidney to responses evoked by angiotensin II (ANG II), endothelin-1 (ET-1), arginine vasopressin (AVP), carbocyclic thromboxane A2 (CTxA2), phenylephrine (PE), and 5-hydroxytryptamine (5-HT). On the basis of their ED50 values (dose of agonist, in mass units, that produced 50% of maximal response to that agonist), the order of vasoconstrictor potency was ANG II > or = AVP > ET-1 > CPA > 5-HT > or = PE > CTxA2. Dose-response curves to CPA were shallower and maximal responses were weaker than those produced by the other agonists. Maximal responses, the log ED50, and the slope of the dose-response curve to CPA were markedly potentiated in the presence of the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME). Selective antagonism of A1 receptors increased renal blood flow and markedly attenuated CPA-induced renal vasoconstriction in the absence or presence of L-NAME but had no effect on the maximal responses to ANG II. Conversely, AT1 receptor antagonism attenuated renal vasoconstriction produced by ANG II but had little effect on the produced by CPA. These results suggest that endogenous NO modulates renal vasoconstriction produced by A1 receptor stimulation and provide evidence against an interaction between renovascular adenosine A1 and angiotensin AT1 receptors.
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PMID:Interactions of adenosine A1 receptor-mediated renal vasoconstriction with endogenous nitric oxide and ANG II. 823 45

This study was performed to evaluate the contribution of angiotensin II to the effects of nitric oxide (NO) synthesis inhibition on renal hemodynamics and excretory function in rats. Intravenous infusion of N omega-nitro-L-arginine (NLA; 20 micrograms/100 g.min) increased renal arterial pressure (RAP) from 128 +/- 2 to 143 +/- 3 mm Hg (P < 0.05; N = 6) and decreased RBF by 64 +/- 3% (P < 0.01) and GFR by 41 +/- 5% (P < 0.05). In response to reduction of RAP to control levels (127 +/- 2 mm Hg) by means of an adjustable clamp (CL) placed on the suprarenal aorta, RBF and GFR exhibited efficient autoregulation and were not altered. In rats (N = 6) pretreated with the AT1 angiotensin II receptor antagonist losartan (10 mg/kg iv), the infusion of NLA increased RAP (from 114 +/- 1 to 135 +/- 2 mm Hg; P < 0.05) and decreased RBF by 42 +/- 3% (P < 0.05). However, NLA did not decrease GFR in the losartan-treated rats. As in the control rats, the reduction of RAP to 113 +/- 1 mm Hg elicited autoregulatory responses that maintained RBF and GFR. In the untreated rats, at similar RAP (128 +/- 2 (control) versus 127 +/- 2 mm Hg (NLA+CL)). NO synthesis inhibition decreased urine flow and sodium excretion (P < 0.05, in both cases). However, during blockade of AT1 receptors, NLA infusion failed to decrease urine flow and sodium excretion, even when RAP was controlled (114 +/- 1 (control) versus 113 +/- 1 mm Hg (NLA+CL)).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Contribution of angiotensin II to renal hemodynamic and excretory responses to nitric oxide synthesis inhibition in the rat. 828 13

The present study was designed to investigate whether nitric oxide (NO) antagonizes angiotensin II (Ang II) in modulating the tubuloglomerular feedback (TGF) system. Maximum TGF responses were assessed by evaluating stop-flow pressure (SFP) responses to late proximal perfusion with artificial tubular fluid (40 nl/min). Peritubular capillary (PTC) infusion of 10(-3) M NG-L-arginine (NLA) at a rate of 20 nl/min, and infusion of 10(-7) and 10(-6) M Ang II at rates that did not decrease SFP under conditions of zero flow to the macula densa (resting SFP), augmented maximum SFP feedback responses to 12.0 +/- 1.7, 12.1 +/- 2.4 and 16.9 +/- 3.0 mm Hg, respectively (all P < 0.01 vs. control response). Combined PTC infusion of NLA and 10(-7) M Ang II at a rate of 20 nl/min resulted in decreases in resting SFP in 7 of the 12 nephrons studied. When the infusion rate was decreased to 15 +/- 3 nl/min, concomitant PTC infusion of NLA and 10(-7) M Ang II was associated with a tremendous increase in maximum TGF responses (23.8 +/- 3.9 mm Hg; P < 0.01 vs. responses during PTC NLA or Ang II) in the absence of a decrease in resting SFP. During AT1 receptor blockade using losartan, SFP feedback responses were attenuated to 1.6 +/- 0.6 mm Hg and PTC infusion of NLA only augmented TGF responses to 3.8 +/- 1.0 mm Hg. These results strongly suggest that local NO antagonizes Ang II with respect to the regulation of TGF responsiveness. Disruption of this balance by NO synthesis inhibition strongly potentiates TGF-independent and TGF-dependent actions of Ang II on the preglomerular vasculature.
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PMID:Nitric oxide antagonizes the actions of angiotensin II to enhance tubuloglomerular feedback responsiveness. 854 96

1. It has been recently reported that angiotensin II can enhance atrial natriuretic factor-stimulated cyclic GMP release from brain capillary endothelial cells and stimulate directly the release of cyclic GMP by Neuro 2a cells. A possible mechanism mediating such cyclic GMP release could be via the production of nitric oxide and the resultant stimulation of soluble guanylate cyclase. 2. The ability of angiotensin II, atrial natriuretic factor and c(4-23) atrial natriuretic factor to stimulate nitric oxide production was investigated in primary cultures of human proximal tubular cells. 3. Freshly prepared human proximal tubular cells were seeded onto 6-well plates and allowed to reach confluence. Cells were then incubated with incremental concentrations of either angiotensin II, atrial natriuretic factor or c(4-23) atrial natriuretic factor alone for 1, 4, 12 or 24h or in the presence of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine. Angiotensin II was also incubated with human proximal tubular cells in the presence of the AT1 and AT2 receptor antagonists DuP 753 and PD 123319. 4. Incubation of human proximal tubular cells with angiotensin II, atrial natriuretic factor or c(4-23) atrial natriuretic factor produced a dose- and time-dependent increase in nitric oxide production, which was inhibited in the presence of NG-monomethyl-L-arginine. A similar increase in nitric oxide production was observed after incubation with atrial natriuretic factor or c(4-23) atrial natriuretic factor. 5. The angiotensin-induced increase in nitric oxide production was not inhibited in the presence of either the angiotensin AT1 or AT2 receptor antagonists DuP 753 or PD 123319. 6. This study demonstrates that primary cultures of human proximal tubular cells can be stimulated to produce nitric oxide by both atrial natriuretic factor and angiotensin II. Furthermore, the atrial natriuretic factor-induced response appears to be mediated via the atrial natriuretic factor-C receptor, while the angiotensin II-induced response appears to be mediated by a novel, as yet unidentified, angiotensin II receptor.
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PMID:Atrial natriuretic factor and angiotensin II stimulate nitric oxide release from human proximal tubular cells. 854 68


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