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)

It has been suggested that low concentrations of angiotensin II cause vasoconstriction, whereas high concentrations evoke vasodilation. Thus, this work aimed to characterize functionally the mechanisms underlying angiotensin II-induced relaxation, at high concentration, in isolated rat aortic rings. Vascular reactivity experiments, using standard muscle bath procedures, showed that angiotensin II (1-30 microM) concentration-dependently induces relaxation of phenylephrine-precontracted rings with intact or denuded endothelium. The relaxation was not altered in the presence of ethylenediamine tetraacetic acid (EDTA), a nonselective inhibitor of metalloprotease. The selective antagonist of AT2 receptors, PD123319, inhibited angiotensin II-induced relaxation. Conversely, losartan or A-779, selective AT1 and Ang1-7 receptor antagonists, respectively, did not alter the relaxation induced by angiotensin II. HOE-140, a selective antagonist of the bradykinin B2 receptor, and amiloride, a Na+/H+ exchanger inhibitor, abolished angiotensin II-induced relaxation. Administration of exogenous bradykinin on precontracted tissues produced concentration-dependent relaxation, which was also inhibited by HOE-140. Preincubation of denuded-rings with NG-nitro-L-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), indomethacin, or tetraethylammonium (TEA) reduced angiotensin II-induced relaxation. The combination of L-NAME, indomethacin, and TEA completely abolished the relaxation induced by angiotensin II. 4-Aminopyridine (4-AP) as well as charybdotoxin reduced angiotensin II-induced relaxation. On the other hand, neither apamin nor glibenclamide altered the relaxation induced by angiotensin II. The major new finding of this work is that it demonstrated functionally the existence of AT2 receptors located on smooth muscle of rat aortic rings that mediated vasorelaxation via stimulation of B2 receptors by bradykinin, which in turns results in the activation of the NO-cGMP pathway, vasodilator cyclooxygenase product(s), and voltage-dependent and Ca+-activated large-conductance K+ channels.
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PMID:Mechanisms underlying the endothelium-independent relaxation induced by angiotensin II in rat aorta. 1565 62

The octapeptide angiotensin II (ANG II) plays a pivotal role in the maintenance of blood pressure by activating ANG II receptors located in variety of cell types including neurons housed in the central nervous system (CNS) and in the peripheral nervous system (PNS). ANG II (100 nM) blocked spike frequency accommodation (SFA) recorded with whole-cell patch technique in acutely isolated nodose ganglion neurons (NGN) from adult rats. ANG II increased the frequency of action potentials (AP) produced by supramaximal 500 ms depolarizing currents recorded in both tonic (16 Hz vs. 58 Hz, control vs. ANG II perfusion respectively, n=9) and phasic (1Hz vs. 38 Hz, n=13) NGNs. ANG II produced no significant changes in: the resting membrane potential (-51 mV vs. -50 mV, n=65), AP overshoot (46 mV vs. 41 mV, n=25), AP undershoot (-65 mV vs. -61 mV, n=25), AP duration (1 ms vs. 1.2 ms, n=25), and AP threshold (-40 mV vs. -43 mV, n=19). CV-11974 (600 nM), a specific AT1 receptor antagonist, prevented ANG II-evoked changes SFA (n=10). ANG II (100 nM) had no significant effect on total outward potassium current (I(K)) but inhibited a fast activating and fast inactivating I(K) recorded in the presence of TEA. A kinetically similar I(K) was also inhibited by 4-AP (3mM). In phasic NGNs, 4-AP occluded the effects of 100 nM ANG II on SFA. Our results indicate that ANG II can block an A-type of I(K) and that this effect may underlie the ANG II-mediated change in SFA.
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PMID:Angiotensin II increases excitability and inhibits a transient potassium current in vagal primary sensory neurons. 1943 35