Gender differences in the endothelial regulation of α2-adrenoceptor-mediated contraction in the rat aorta

1999 ◽  
Vol 97 (1) ◽  
pp. 19-25 ◽  
Author(s):  
Nuria TEJERA ◽  
Gloria BALFAGÓN ◽  
Jesús MARÍN ◽  
Mercedes FERRER
Keyword(s):  
Rank Order ◽  
Rat Aorta ◽  
Ovariectomized Rats ◽  
Maximal Response ◽  
Nitric Oxide Synthase Inhibitor ◽  
Adrenoceptor Antagonist ◽  
Α2 Adrenoceptor ◽  
No Release ◽  
Synthase Inhibitor ◽  
Oxide Synthase

The aim of this study was to determine the possible influence of sex hormones on the contractile responses induced by clonidine, an agonist of α2-adrenoceptors, as well as the endothelial modulation of these responses. For this purpose, thoracic aorta segments from male (control and castrated) and female (in oestrous phase and ovariectomized) rats were used. In intact segments from the four groups of rats, clonidine (0.01-10 µmol/l) induced concentration-dependent contractions, which were increased by the nitric oxide synthase inhibitor Nω-nitro-⌊-arginine methyl ester (0.1 mmol/l) or by endothelium removal, but were reduced by 1 µmol/l yohimbine (an α2-adrenoceptor antagonist) in all animals and by 1 µmol/l indomethacin (a cyclo-oxygenase inhibitor) in control males only. The rank order of the magnitude of the maximal response was: oestrous females > ovariectomized females > control males > castrated males, whereas the sensitivity to clonidine (EC50 value) was similar in all animals. In endothelium-denuded segments, the rank order was: oestrous females = control males > ovariectomized females = castrated males. These results suggest that: (1) the presence of oestrogen or androgen increases the contraction caused by α2-adrenoceptor activation with clonidine; (2) endothelium negatively modulates the response to this agonist in the four groups of rats, due to endothelial NO release (entirely in females and in part in males); (3) androgen also seems to modulate the response by stimulating the release of an endothelial contracting factor, probably a prostanoid; and (4) the endothelium of males has a greater capacity than that of comparable females for negative regulation of the tension generated by the underlying vascular smooth muscle.

Nitric oxide modulates arteriolar responses to increased sympathetic nerve activity

1996 ◽  
Vol 271 (3) ◽  
pp. H860-H869 ◽  
Author(s):  
G. P. Nase ◽  
M. A. Boegehold
Keyword(s):  
Nitric Oxide ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Nerve Activity ◽  
Nitric Oxide Synthase Inhibitor ◽  
Alpha Adrenoceptor ◽  
Adrenoceptor Antagonist ◽  
Endogenous Nitric Oxide ◽  
Synthase Inhibitor ◽  
Oxide Synthase

The purpose of this study was to determine whether arteriolar responses to increased sympathetic nerve activity are limited by the actions of endogenous nitric oxide. Intravital microscopy was used to examine diameter responses of small feed arteries (SFA), first-order arterioles (1A) and second-order arterioles (2A) to perivascular sympathetic nerve stimulation in the superfused rat small intestine. Stimulation induced a frequency-dependent constriction in all vessel types that was completely abolished by the alpha-adrenoceptor antagonist phentolamine (10(-6) M). In SFA and 1A, the magnitude of sympathetic constriction was increased significantly in the presence of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine(L-NMMA, 10(-4) M). In SFA (n = 7), stimulation at 3, 8, and 16 Hz induced constrictions of 11 +/- 1, 28 +/- 4, and 42 +/- 3%, respectively, under the normal superfusate vs. 28 +/- 3, 46 +/- 5, and 76 +/- 3% in the presence of L-NMMA. For 1A (n = 7), stimulation induced constrictions of 10 +/- 1, 27 +/- 4, and 37 +/- 3% under the normal superfusate vs. 24 +/- 2, 47 +/- 3, and 72 +/- 4% in the presence of L-NMMA. The effect of L-NMMA on sympathetic constriction in SFA (n = 7) was completely reversed by the additional presence of 5 x 10(-3) M L-arginine in the superfusate. These results suggest that endogenous nitric oxide activity can attenuate sympathetic neurogenic constriction in the intestinal microvasculature.

scholarly journals Ca2+ influx mediates enhanced α2-adrenergic contraction in aortas from rats treated with NOS inhibitor

2001 ◽  
Vol 281 (5) ◽  
pp. H2233-H2240 ◽  
Author(s):  
Harshini Mukundan ◽  
Nancy L. Kanagy
Keyword(s):  
Calcium Imaging ◽  
Rat Aorta ◽  
Nitric Oxide Synthase Inhibitor ◽  
Voltage Dependent Calcium Channel ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
Nos Inhibitor ◽  
The Common ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Previously, we reported that aortic segments from rats made hypertensive with the nitric oxide synthase inhibitor N ω-nitro-l-arginine (l-NNA) exhibit enhanced contractile sensitivity to both α2-adrenergic receptor (α2-AR) stimulation and to KCl-induced depolarization. We hypothesized that increased contractile responses to these agents was due to a change in the common effector L-type voltage-dependent calcium channel (VDCC). In aortic segments from control and l-NNA-treated rats, contraction to the α2-AR agonist UK-14304 stimulated Ca2+influx but released intracellular Ca2+ only in control arteries. UK-14304-induced contraction was blocked by the VDCC antagonist nifedipine in both control and l-NNA aortas but contraction of aortas from l-NNA-treated rats was blocked by lower concentrations. Calcium imaging studies in fura 2-loaded freshly isolated aortic vascular smooth muscle cells also demonstrated UK-14304-stimulated Ca2+ influx sensitive to nifedipine only in cells from l-NNA-treated rats. We conclude that α2-AR contraction in the rat aorta is mediated primarily by Ca2+ influx and that l-NNA-induced hypertension increases the dependence of this contraction on VDCCs.

Halothane Attenuates Endothelium-dependent Pulmonary Vasorelaxant Response to Lemakalim, an Adenosine Triphosphate (ATP)-sensitive Potassium Channel Agonist

1997 ◽  
Vol 87 (3) ◽  
pp. 625-634 ◽  
Author(s):  
Sumihiko Seki ◽  
Mayumi Horibe ◽  
Paul A. Murray
Keyword(s):  
Adenosine Triphosphate ◽  
Inhibitory Effect ◽  
Isometric Tension ◽  
Maximal Response ◽  
Response Curves ◽  
Nitric Oxide Synthase Inhibitor ◽  
Pulmonary Vasodilation ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
Channel Agonist

Background Lemakalim, an adenosine triphosphate (ATP)-sensitive potassium (K+(ATP)) channel agonist, causes profound pulmonary vasodilation in conscious dogs, which is attenuated during halothane anesthesia. The goal of the present study was to investigate the mechanism responsible for this attenuating effect of halothane. Methods Isolated canine pulmonary arterial rings were suspended for isometric tension recording in 25 ml organ baths. Rings with and without endothelium were contracted to 50% of their maximal response to phenylephrine, followed by the cumulative administration of lemakalim with or without exposure to halothane (0.5-1.5 minimum alveolar concentration [MAC] in dogs). Lemakalim dose-response curves were also generated in rings pretreated with the nitric oxide synthase inhibitor, Nw-nitro-L-arginine methyl ester (L-NAME); the cyclooxygenase inhibitor, indomethacin; or the K+(ATP) channel antagonist, glybenclamide. Results Compared with intact rings, the pulmonary vasorelaxant response to lemakalim was attenuated (P < 0.05) in endothelium-denuded rings. Halothane at 0.5 MAC had no effect on the vasorelaxant response to lemakalim. Halothane at 1 MAC attenuated (P < 0.05) the vasorelaxant response to lemakalim in intact rings, but not in endothelium-denuded rings. Halothane at 1.5 MAC attenuated (P < 0.05) the vasorelaxant response to lemakalim in both intact and endothelium-denuded rings. In endothelium-intact rings, indomethacin attenuated (P < 0.05) the vasorelaxant response to lemakalim, whereas L-NAME had no effect. Further, indomethacin, but not L-NAME, abolished the endothelium-dependent, halothane-induced attenuation of the lemakalim vasorelaxation response. Glybenclamide markedly attenuated (P < 0.05) lemakalim vasorelaxation at lemakalim doses less than 10(-6) M. Conclusions Lemakalim-induced pulmonary vasorelaxation involves an endothelium-dependent and vascular smooth muscle component. Further, halothane attenuates the endothelium-dependent pulmonary vasorelaxant response to lemakalim via an inhibitory effect on vasodilator metabolites of the cyclooxygenase pathway.

Acrolein-induced vasomotor responses of rat aorta

2003 ◽  
Vol 285 (2) ◽  
pp. H727-H734 ◽  
Author(s):  
Nina L. Tsakadze ◽  
Sanjay Srivastava ◽  
Sunday O. Awe ◽  
Ayotunde S. O. Adeagbo ◽  
Aruni Bhatnagar ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Rat Aorta ◽  
Nitric Oxide Synthase Inhibitor ◽  
Vasomotor Responses ◽  
Endothelial Denudation ◽  
Synthase Inhibitor ◽  
Resting Tone ◽  
Oxide Synthase ◽  
Dose Dependent

Acrolein is a highly reactive aldehyde pollutant and an endogenous product of lipid peroxidation. Increased generation of, or exposures to, acrolein incites pulmonary and vascular injury. The effects of acrolein on the vasomotor responses of rat aortic rings were studied to understand its mechanism of action. Incubation with acrolein (10–100 μM) alone did not affect the resting tone of aortic vessels; however, a dose-dependent relaxation of phenylephrine-precontracted aortic rings was observed. Acrolein-induced relaxation was slow and time dependent and the extent of relaxation after 100 min of application was 44.7 ± 4.1% (10 μM), 56.0 ± 5.6% (20 μM), 61.0 ± 7.9% (40 μM), and 96.1 ± 2.1 (80 μM), respectively, versus 14.2 ± 3.3% relaxation in the absence of acrolein. Acrolein-induced vasorelaxation was prevented by endothelial denudation and was abolished on pretreatment with the nitric oxide synthase inhibitor Nω-nitro-l-arginine methyl ester, the guanylyl cyclase inhibitor 1 H-[1,2,4]oxidazolo[4,3- a]quinoxaline-1-one, or the cyclooxygenase inhibitor indomethacin. Inhibition of K+ channels (by tetrabutylammonium) or Na+-K+-ATPase (by ouabain) did not significantly prevent acrolein-mediated vasorelaxation. Exposure to acrolein in the presence or absence of other compounds elicited slow wave vasomotor effect in 77% of aortic vessels versus 1.4% in control. Vasomotor responses were also studied on aortic rings prepared from rats fed 2 mg · kg–1 · day–1 acrolein for 3 alternate days by oral gavage. These vessels developed a significantly lower contractile response to phenylephrine compared with controls. Together, these results indicate that acute acrolein exposure evokes delayed vasorelaxation due to a nitric oxide- and prostacyclin-dependent mechanism, whereas in vivo acrolein exposure compromises vessel contractility.

Glomerular and tubular interactions between renal adrenergic activity and nitric oxide

1995 ◽  
Vol 268 (6) ◽  
pp. F1004-F1008 ◽  
Author(s):  
F. B. Gabbai ◽  
S. C. Thomson ◽  
O. Peterson ◽  
L. Wead ◽  
K. Malvey ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Glomerular Filtration ◽  
Renal Nerves ◽  
Ang Ii ◽  
Nitric Oxide Synthase Inhibitor ◽  
Adrenergic Activity ◽  
Single Nephron ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Endothelium-dependent nitric oxide (EDNO) exerts control over the processes of glomerular filtration and tubular reabsorption. The importance of the renal nerves to the tonic influence of EDNO in the glomerular microcirculation and proximal tubule was tested by renal micropuncture in euvolemic adult male Munich-Wistar rats. The physical determinants of glomerular filtration and proximal reabsorption were assessed before and during administration of the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA), in control animals and in animals 5–9 days after either ipsilateral surgical renal denervation (DNX) or after either sham surgery (SHX). L-NMMA caused single-nephron glomerular filtration rate to decline in control and SHX animals but not in DNX rats. L-NMMA caused a reduction in proximal reabsorption in control and SHX rats, which was prevented by prior DNX. DNX did not alter urinary guanosine 3',5'-cyclic monophosphate excretion, and, although DNX upregulates glomerular angiotensin II (ANG II) receptors, prior DNX did not alter intrarenal ANG II content as evaluated by radioimmunoassay. Some component of renal adrenergic activity is required for the full expression of the glomerular and tubular effects of blockade of nitric oxide synthase.

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