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)

Stimulated release of vasodilator prostaglandins and nitric oxide by angiotensin II may counteract the vasoconstrictor effects of this octapeptide. We investigated the effects of inhibition of prostaglandin synthesis by indomethacin and of nitric oxide formation by NG-monomethyl-L-arginine (L-NMMA) on baseline forearm blood flow (FBF) and on angiotensin II-induced vasoconstriction in healthy subjects. For comparison, the effects of the AT1-receptor antagonist losartan on these parameters were determined. FBF was measured by venous occlusion plethysmography. Angiotensin II (0.01-10 ng/kg/min) was infused into the brachial artery, in the absence and presence of indomethacin (0.65 micrograms/kg/min; n = 8), L-NMMA (30 micrograms/kg/min; n = 5), and losartan (3 micrograms/kg/min; n = 12), respectively. Sodium nitroprusside was used to submaximally predilate the forearm vascular system. Baseline FBF remained unchanged with indomethacin and losartan, but was significantly decreased by -42 +/- 6% (mean +/- SEM) by L-NMMA. The dose-dependent angiotensin II-induced vasoconstriction was unaffected by indomethacin and L-NMMA, but was inhibited by losartan. Emax was -78 +/- 2% during control conditions, -84 +/- 3% during indomethacin (n.s.), -74 +/- 4% during L-NMMA (n.s.), and -17 +/- 6% during losartan infusion (p < 0.05). None of the interventions significantly changed the EC50 value of angiotensin II of -9.4 +/- 0.14 log M. In conclusion, in the human forearm of healthy subjects, neither endogenous angiotensin II nor cyclooxygenase-dependent prostaglandin synthesis plays a role in the genesis of vascular tone, whereas endogenous nitric oxide production does. The constrictor effects of angiotensin II are counteracted by neither stimulated release of prostaglandins nor by that of nitric oxide.
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PMID:Influence of indomethacin and L-NMMA on vascular tone and angiotensin II-induced vasoconstriction in the human forearm. 935 98

Arterial constriction by angiotensin II (Ang II) in the human forearm is inhibited by the infusion of the AT1-receptor antagonist losartan. We investigated venous constriction by Ang II in the forearm of 19 healthy subjects (23 +/- 1 years) and the inhibitory effects of losartan. Furthermore, we investigated, in both the arterial and venous systems, whether the constrictor effects of Ang II are calcium influx dependent by determining the influence of nicardipine. Arterial forearm blood flow (FBF) and maximal venous outflow (MVO) were measured by venous-occlusion plethysmography. Sodium nitroprusside (5-12.5 ng/kg/min) was infused to predilate the forearm vasculature. Ang II (0.1, 1, and 10 ng/kg/min) was infused before and during losartan (0.3 and 3 microg/kg/min) or nicardipine (0.05 and 0.15 microg/kg/min), respectively. Ang II decreased FBF (Emax-FBF) by 79 +/- 4% and MVO (Emax-MVO) by 28 +/- 3% (p < 0.05). Nicardipine at 0.05 and 0.15 microg/kg/min reduced Emax-FBF from -79 +/- 4% to -48 +/- 4% and -6 +/- 2%, respectively (p < 0.05). Losartan in both doses completely inhibited Emax-MVO (p < 0.05), whereas nicardipine did not influence the venoconstriction by Ang II (p > 0.05). In conclusion, Ang II causes a constriction of both arteries and veins in the human forearm, which may be inhibited by losartan. The arterial constriction appears to be caused by an AT1-receptor-mediated calcium influx via L-type calcium channels. In contrast, the venoconstrictor effect of Ang II proved insensitive to the calcium antagonist nicardipine.
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PMID:Venoconstriction by angiotensin II in the human forearm is inhibited by losartan but not by nicardipine. 945 77

We demonstrated that the decreased response to acetylcholine observed in aorta of male and female spontaneously hypertensive rats is corrected after sustained (15 days) reduction of blood pressure levels by losartan. In order to verify if the same occurs in resistance vessels, vascular diameter changes induced by topical application of acetylcholine and bradykinin (endothelium-dependent vasodilators) and sodium nitroprusside (endothelium-independent vasodilator) to mesenteric arterioles studied in vivo, in situ were determined in rats treated with losartan for 24 h (acute) or 15 days (chronic). Rats that presented similar reduction (in %) of the blood pressure levels after losartan treatment were chosen. Sodium nitroprusside induced similar responses in losartan-treated and untreated male or female SHR. Whereas in female SHR, losartan corrected the diminished arteriolar response to endothelium-dependent vasodilators after acute and chronic treatment, in male SHR this correction only occurred after chronic treatment. Thus, losartan corrected the endothelial dysfunction more easily in female than in male SHR and independently of the normalization or the magnitude of the reduction of the blood pressure levels. In an attempt to explain the difference, we evaluated the losartan effect on nitric-oxide synthase (NOS) activity and angiotensin II AT1 and AT2 receptor gene expression in these animals. In male and female SHR, NOS activity and AT1 receptor expression were not altered by acute or chronic treatment. On the other hand, AT2 receptor expression was augmented only in female SHR by these treatments. Therefore, augmented AT2 receptor expression, but not alteration of NOS activity or AT1 receptor expression, might explain the difference observed.
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PMID:Differential effect of losartan in female and male spontaneously hypertensive rats. 1633 58