Impairment of nitric oxide synthase-dependent dilatation of cerebral arterioles during infusion of nicotine

2003 ◽  
Vol 284 (2) ◽  
pp. H528-H534 ◽  
Author(s):  
Qin Fang ◽  
Hong Sun ◽  
William G. Mayhan
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Nitric Oxide Synthase ◽  
Maintenance Dose ◽  
Oxygen Radicals ◽  
Cerebral Vessels ◽  
Before And After ◽  
Pial Arterioles ◽  
Cerebral Arterioles ◽  
Oxide Synthase

The effects of nicotine on nitric oxide synthase (NOS)-dependent reactivity of cerebral arterioles remain uncertain. Our first goal was to examine whether infusion of nicotine alters NOS-dependent reactivity of cerebral arterioles. Our second goal was to examine the mechanisms that may account for the effects of nicotine on cerebral arterioles. We measured the diameter of pial arterioles to NOS-dependent (ADP and acetylcholine) and NOS-independent (nitroglycerin) agonists before and after the infusion of nicotine (2 μg · kg−1· min−1iv for 30 min, followed by a maintenance dose of 0.35 μg · kg−1· min−1). ADP- and acetylcholine-induced vasodilatation was impaired after the infusion of nicotine. In contrast, nicotine did not alter vasodilatation to nitroglycerin. Next, we examined whether the impaired responses of pial arterioles during infusion of nicotine may be related to oxygen radicals. We found that application of superoxide dismutase or tetrahydrobiopterin during infusion of nicotine could prevent impaired NOS-dependent vasodilatation. Thus acute exposure of cerebral vessels to nicotine specifically impairs NOS-dependent dilatation via the production of oxygen radicals possibly related to an alteration in the utilization of tetrahydrobiopterin.

Effects of ischemia on cerebrovascular responses to N-methyl-D-aspartate in piglets

1996 ◽  
Vol 270 (4) ◽  
pp. H1225-H1230 ◽  
Author(s):  
D. W. Busija ◽  
W. Meng ◽  
F. Bari ◽  
P. S. McGough ◽  
R. A. Errico ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Smooth Muscle ◽  
Intracranial Pressure ◽  
Nitric Oxide Synthase ◽  
Before And After ◽  
Newborn Pigs ◽  
Oxide Synthase ◽  
Enhanced Degradation

We examined the effects of total global ischemia on cerebral arteriolar responses to N-methyl-D-aspartate (NMDA) in anesthetized newborn pigs. Arteriolar responses to 10(-4) M NMDA were determined before and after 10 to 20 min of ischemia caused by increasing intracranial pressure. Before ischemia, NMDA dilated arterioles by 30 +/- 5% (baseline = 88 +/- 2 microns; n = 6). However, after 10 min of ischemia, arteriolar dilation was reduced to 10 +/- 3% at 1 h (P < 0.05). At 2 and 4 h, NMDA-induced dilation was not different from preischemia values. Twenty minutes of ischemia had similar effects. Coadministration of 100 U/ml of superoxide dismutase did not restore arteriolar dilation to NMDA at 1 h after ischemia. Sodium nitroprusside dilated by 14 +/- 3 and 40 +/- 5% at 10(-6) and 10(-5) M before ischemia, respectively, and arteriolar responsiveness was not changed by ischemia (n = 6). Cortical nitric oxide synthase (NOS) activity, measured by the in vitro conversion of L-[14C]arginine to L-[14C]citrulline, was unaffected by ischemia (n = 12). We conclude that decreases in cerebral arteriolar responsiveness to NMDA are not due to impairment of NOS activity, enhanced degradation or chelation of nitric oxide (NO), or reduced vascular smooth muscle responsiveness to NO.

Nicotine impairs histamine-induced increases in macromolecular efflux: role of oxygen radicals

1998 ◽  
Vol 84 (5) ◽  
pp. 1589-1595 ◽  
Author(s):  
William G. Mayhan ◽  
Glenda M. Sharpe
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Smokeless Tobacco ◽  
Oxygen Radicals ◽  
Cheek Pouch ◽  
Hamster Cheek Pouch ◽  
Macromolecular Transport ◽  
Before And After ◽  
Oxide Synthase

Nicotine, a major component of cigarettes and smokeless tobacco, has toxic effects on endothelium and impairs reactivity of resistance arterioles in response to agonists that stimulate the synthesis and/or release of nitric oxide. However, the effect of nicotine on nitric oxide synthase-dependent increases in macromolecular transport is not known. Thus our first goal was to determine the effect of nicotine on histamine-induced increases in macromolecular efflux. We used intravital microscopy and FITC dextran (mol wt 70,000) (FITC-dextran-70K) to examine macromolecular extravasation from postcapillary venules in response to histamine before and after intravenous infusion of vehicle or nicotine. Extravasation of macromolecules was quantitated by counting venular leaky sites and calculating clearance (ml/s × 10−6) of FITC-dextran-70K. Histamine elicited reproducible increases in venular leaky sites and clearance in hamsters infused with vehicle. In contrast, nicotine infusion inhibited histamine-induced increases in macromolecular efflux. Histamine (1.0 and 5.0 μM) elicited 19 ± 2 and 34 ± 4 vs. 3 ± 1 and 11 ± 5 leaky sites per 0.11 cm2, before vs. after nicotine infusion, respectively ( P < 0.05). Histamine-induced clearance of FITC-dextran-70K was also impaired after infusion of nicotine. Our second goal was to examine whether alterations in histamine-induced increases in macromolecular efflux by nicotine may be related to the production of oxygen radicals. Application of superoxide dismutase (150 U/ml) to the hamster cheek pouch restored histamine-induced increases in venular leaky sites and clearance of FITC-dextran-70K during infusion of nicotine. Thus nicotine alters agonist-induced increases in microvascular permeability, via the formation of oxygen radicals, to presumably inactivate nitric oxide.

Are Superoxide Dismutase 2 and Nitric Oxide Synthase Polymorphisms Associated with Idiopathic Infertility?

2014 ◽  
Vol 21 (4) ◽  
pp. 565-569 ◽  
Author(s):  
Celine Faure ◽  
Pauline Leveille ◽  
Charlotte Dupont ◽  
Chantal Julia ◽  
Pascale Chavatte-Palmer ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Nitric Oxide Synthase ◽  
Idiopathic Infertility ◽  
Oxide Synthase ◽  
Superoxide Dismutase 2

Inhibition of tetrahydrobiopterin biosynthesis impairs endothelium-dependent relaxations in canine basilar artery

1997 ◽  
Vol 273 (2) ◽  
pp. H718-H724 ◽  
Author(s):  
H. Kinoshita ◽  
S. Milstien ◽  
C. Wambi ◽  
Z. S. Katusic
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Nitric Oxide Synthase ◽  
Endothelial Function ◽  
Isometric Force ◽  
Cerebral Arteries ◽  
Calcium Ionophore ◽  
Nitric Oxide Donor ◽  
Ionophore A23187 ◽  
Oxide Synthase

Tetrahydrobiopterin is an essential cofactor in biosynthesis of nitric oxide. The present study was designed to determine the effect of decreased intracellular tetrahydrobiopterin levels on endothelial function of isolated cerebral arteries. Blood vessels were incubated for 6 h in minimum essential medium (MEM) in the presence or absence of a GTP cyclohydrolase I inhibitor, 2,4-diamino-6-hydroxypyrimidine (DAHP, 10(-2) M). Rings with and without endothelium were suspended for isometric force recording in the presence of a cyclooxygenase inhibitor, indomethacin (10(-5) M). In arteries with endothelium, DAHP significantly reduced intracellular levels of tetrahydrobiopterin. DAHP in combination with a precursor of the salvage pathway of tetrahydrobiopterin biosynthesis, sepiapterin (10(-4) M), not only restored but increased levels of tetrahydrobiopterin above control values. In DAHP-treated arteries, endothelium-dependent relaxations to bradykinin (10(-10)-10(-6) M) or calcium ionophore A23187 (10(-9)-10(-6) M) were significantly reduced, whereas endothelium-independent relaxations to a nitric oxide donor, 3-morpholinosydnonimine (10(-9)-10(-4) M), were not affected. When DAHP-treated arteries with endothelium were incubated with sepiapterin (10(-4) M) or superoxide dismutase (150 U/ml), relaxations to bradykinin and A23187 were restored to control levels. In contrast, superoxide dismutase did not affect endothelium-dependent relaxations in arteries incubated in MEM. A nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (10(-4) M), abolished relaxations to bradykinin or A23187 in control arteries and in DAHP-treated arteries. These studies demonstrate that in cerebral arteries, decreased intracellular levels of tetrahydrobiopterin can reduce endothelium-dependent relaxations. Production of superoxide anions during activation of dysfunctional endothelial nitric oxide synthase appears to be responsible for the impairment of endothelial function.

scholarly journals The Key Role of Caveolin-1 in Estrogen-Mediated Regulation of Endothelial Nitric Oxide Synthase Function in Cerebral Arterioles In vivo

2001 ◽  
Vol 21 (8) ◽  
pp. 907-913 ◽  
Author(s):  
Hao-Liang Xu ◽  
Elena Galea ◽  
Roberto A. Santizo ◽  
Verna L. Baughman ◽  
Dale A. Pelligrino
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Functional Activity ◽  
Endothelial Nitric Oxide Synthase ◽  
Down Regulation ◽  
Caveolin 1 ◽  
Cerebral Arterioles ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

The marked impairment in cerebrovascular endothelial nitric oxide synthase (eNOS) function that develops after ovariectomy may relate to the observation that the abundance of cerebral vascular eNOS and its endogenous inhibitor, caveolin-1, vary in opposite directions with chronic changes in estrogen status. The authors endeavored, therefore, to establish a link between these correlative findings by independently manipulating, in ovariectomized female rats, eNOS and caveolin-1 expression, while monitoring agonist (acetylcholine)-stimulated eNOS functional activity. In the current study, the authors showed that individually neither the up-regulation of eNOS (through simvastatin treatment), nor the down-regulation of caveolin-1 (through antisense oligonucleotide administration) is capable of restoring eNOS function in pial arterioles in vivo in these estrogen-depleted rats. Only when eNOS up-regulation and caveolin-1 down-regulation are combined is activity normalized. These results establish a mechanistic link between the estrogen-associated divergent changes in the abundance of caveolin-1 and eNOS protein and eNOS functional activity in cerebral arterioles.

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