choline. Our findings could also explain
why, in shock lung syndrome, patients
do not always respond to therapy with
certain vasodilator drugs (3).
Irrespective of the exact mechanism,
selective removal of endothelium from
intrapulmonary arteries can transform
two important circulating dilator agents
into pulmonary vasoconstrictors. It is
thus conceivable that damage in vivo to
intrapulmonary arterial and arteriolar en-
dothelial cells or destruction of pulmo-
nary arterial endothelial cells by a num-
ber of agencies acting alone or in concert
(for example, chronic hypoxia, release of
hydrolytic enzymes, leukocyte platelet-
endothelial cell interactions resulting in
release of lysosomal enzymes, microag-
gregation of formed elements adjacent to
these endothelial cells) may represent
the major pathway in producing pulmo-
nary hypertension or shock lung.
Our data may also explain why, in
numerous studies on isolated pulmonary
blood vessels-which are often trauma-
tized in preparation-acetylcholine and
certain other so-called vasodilators will
produce contraction rather than dilation
of these vessels (6).
NARESH CHAND
BURTON M. ALTURA
Department of Physiology, State
University of New York, Downstate
Medical Center, Brooklyn 11203
References and Notes
1. R. F. Furchgott and J. V. Zawadzki, Pharma-
cologist 21, 271 (1979); Fed. Proc. Fed. Am.
Soc. Exp. Biol. 39, 581 (1980); Nature (London)
288, 373 (1980); , P. D. Cherry, in Mecha-
nisms of Vasodilatation, P. M. Vanhoutte and I.
Leusen, Eds. (Raven, New York, in press), vol.
2.
2. J. B. West, Pulmonary Pathophysiology-The
Essentials (Williams & Wilkins, Baltimore,
1977); J. K. Perloff, in Pulmonary Vascular
Disease, K. M. Moser, Ed. (Dekker, New York,
1979), p. 489; M. Voelkel and J. T. Reeves, in
ibid., p. 573.
3. A. P. Thal, E. B. Brown, Jr., A. S. Hermreck,
H. M. Bell, Shock. A Physiologic Basis for
Treatment (Year Book, Chicago, 1971); J. W.
Wilson, in The Cell in Shock (Upjohn, Kalama-
zoo, Mich., 1974), p. 39; B. J. Pardy and H. A.
F. Dudley, Surg. Gynecol. Obstet. 144, 259
(1977).
4. N. Chand and B. M. Altura, J. AppI. Physiol.
49, 1016 (1980); Prostagland. Med. 5, 59 (1980);
B. M. Altura and N. Chand, Br. J. Pharmacol.,
in press.
5. B. M. Altura and B. T. Altura, Am. J. Physiol.
219, 1698 (1970).
6. E. H. Bergofsky, in Pulmonary Vascular Dis-
ease, K. M. Moser, Ed. (Dekker, New York,
1979), p. 233; P. M. Vanhoutte, in Microcircula-
tion, G. Kaley and B. M. Altura, Eds. (Universi-
ty Park Press, Baltimore, 1978), vol. 2, p. 181.
7. Intrapulmonary arteries were fixed in 2 percent
glutaraldehyde and 0.1M potassium phosphate
(pH 7.4) for 60 minutes at 4C, postfixed in I
percent 0,04 and 0.1M potassium phosphate,
dehydrated in a graded ethanol series, and em-
bedded in Epon 812. Thin sections were stained
with uranyl acetate and lead citrate. These were
then examined and photographed in a JEOL
IOOC electron microscope.
8. Supported in part by PHS research grants
NHLBI 18002, NHLBI 18015. and DA 02339 (to
B.M.A.). We thank G. K. Ojakian and D. Herz-
linger for performing the electron microscopy.
Requests for reprints should be addressed to
B.M.A.
16 April 1981; revised 4 June 1981
SCIENCE, VOL. 213, 18 SEPTEMBER 1981
Chiral
Recognition by Nucleosides and Nucleotides: Resolution
of Helicenes by High-Performance Liquid Chromatography
Abstract. Chiral recognition by nucleosides and nucleotides coated on silica gel
was studied by high-performance liquid chromatography. Helicenes, which are
chiral polyaromatic hydrocarbons, were used as probes. Stereoselectivity was
detected when the nucleobase was a purine (adenosine, deoxyadenosine, adenosine
3'-monophosphate, adenosine S'-monophosphate, adenosine 3',5'-monophosphate,
and guanosine), but was not detected with the pyrimidine derivative uridine. For a
given nucleobase (adenine), all changes in the ribose moiety affected the resolution
factors, which ranged between 1.03 and 1.074. These results might be relevant to the
enantioselectivity of carcinogenic metabolites of polyaromatic hydrocarbons.
We recently described enantioselec-
tive interactions of riboflavin with chiral
ortho-condensed polyaromatic hydro-
carbons as manifested in resolutions of
optical isomers by high-performance liq-
uid chromatography (HPLC) (1). We
now report a similar study with nucleo-
sides and nucleotides coated on the col-
umn packing material. As in the ribofla-
vin study (1), helicenes, which have a
helical shape due to overcrowding, were
the compounds resolved. Although heli-
cenes do not occur in nature, the results
may be of interest for probing the capaci-
ty of nucleic acid building blocks for
chiral differentiation.
P(+)-Hexahelicene M(-)-Hexahelicene
The compounds tested were 1, adeno-
sine; 2, deoxyadenosine; 3, adenosine 3'-
monophosphate (3'-AMP); 4, adenosine
5'-monophosphate (5'-AMP); 5, adeno-
sine 3',5'-monophosphate (cyclic AMP);
6, guanosine; and 7, uridine. Purines and
pyrimidines form complexes with poly-
Time (minutes)
aromatic hydrocarbons. Combination of
a purine or pyrimidine with a chiral sub-
stituent such as ribose could lead to
chiral differentiation of optically active
polyaromatic hydrocarbons, in analogy
NO2 NO2 NH2
NO2 NO2 WCN
N
N HOH2C
H-C-CH3
COOH HO OH
R(-)-TAPA Adenosine
with the behavior of R(-)-2-(2,4,5,7-
tetranitrofluorylidene-9-aminooxy)pro-
pionic acid (TAPA) (2) and of riboflavin
(1). The molecular interaction of nucleo-
bases with polyaromatic hydrocarbons
differs from that of TAPA and riboflavin,
since for the nucleobases the contribu-
tion of charge transfer is considered to
be of little importance as compared with
van der Waals forces (3).
The nucleosides and nucleotides were
coated on 5-,um silica gel (Lichrosorb Si
100, Merck, Darmstadt, Germany) and
HPLC columns were prepared by slurry
packing. The amount of coated material,
determined by elementary analysis, var-
Fig. 1. Resolution of the opti-
cal isomers of [101- to [13]-
carbohelicenes on adenosine-
coated silica gel. The number
in brackets indicates the num-
ber of rings in an individual
helicene. The chromatograph-
ic system consisted of a Wa-
ters 6000A pump, a Reodyne
7120 injector with a 20-,Ll loop,
and an LDC ultraviolet moni-
tor set at 254 nm. The column
was 20 by 0.46 cm (inside di-
ameter). The eluant was
CH2Cl2 and n-hexane (1:9);
the flow rate was I ml/min;
, and the temperature 230 to
20 25'C. The elution curves cor-
respond to (A) [101-helicene
enriched in the M(-)isomer,
and (B) [11]-, (C)[12]-, and (D)
[131-helicenes.
0036-8075/81/0918-1379$01.00/0 Copyright © 1981 AAAS 1379
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