helin isopeptides (endothelin-1, endothelin-2 and endothelin-3), which resemble one another in structure, exist in the bodies of animals including human, and these peptides have vasoconstriction and pressor effects (Proc. Natl. Acad, Sci, USA, 86, 2863-2867 (1989)).
As reported, the endothelin levels are clearly elevated in the blood of patients with essential hypertension, acute myocardial infarction, pulmonary hypertension, Raynaud""s disease, diabetes or atherosclerosis, or in the washing fluids of the respiratory tract or the blood of patients with asthmaticus as compared with normal levels (Japan, J. Hypertension, 12, 79, (1989), J. Vascular medicine Biology, 2, 207 (1990), Diabetologia, 33, 306-310 (1990), J. Am. Med. Association, 264, 2868 (1990), and The Lancet, ii, 747-748 (1989) and ii, 1144-1147 (1990)).
Further, an increased sensitivity of the cerebral blood vessel to endothelin in an experimental model of cerebral vasospasm (Japan. Soc. Cereb. Blood Flow and Metabol., 1, 73 (1989)), an improved renal function by the endothelin antibody in an acute renal failure model (J. Clin, invest., 83, 1762-1767 (1989), and inhibition of gastric ulcer development with an endothelin antibody in a gastric ulcer model (Extract of Japanese Society of Experimental Gastric Ulcer, 50 (1991)) have been reported. Therefore, endothelin is assumed to be one of the mediators causing acute renal failure or cerebral vasospasm following subarachnoid hemorrhage.
Further, endothelin is secreted not only by endothelial cells but also by tracheal epithelial cells or by kidney cells (FEBS Letters, 255, 129-132 (1989), and FEBS Letters, 249, 42-46 (1989)).
Endothelin was also found to control the release of physiologically active endogenous substances such as renin, atrial natriuretic peptide, endothelium-derived relaxing factor (EDRF), thromboxane A2, prostacyclin, noradrenaline, angiotensin II and substance P (Biochem. Biophys, Res. Commun., 157, 1164-1168 (1988); Biochem. Biophys, Res.
helin isopeptides (endothelin-1, endothelin-2 and endothelin-3), which resemble one another in structure, exist in the bodies of animals including homo, and these peptide receive vasoconstriction and pressor effect (Proc. Natl. Acad, Sci, USA, 86, 2863 - 2867 (1989) ). 
 As report, the endothelin levels are clearly promote in the blood of patients with all-important hypertension, acute myocardial infarct, pulmonary hypertension, Raynaud""s disease, diabetes or atherosclerosis, or in the washing fluids of the respiratory nerve pathway or the blood of patients with asthmaticus as compare with normal levels (Japan, J. Hypertension, 12, 79, (1989), J. Vascular medicine Biology, 2, 207 (1990), Diabetologia, 33, 306 - 310 (1990), J. Am. Med. Association, 264, 2868 (1990), and The Lancet, ii, 747 - 748 (1989) and ii, 1144 - 1147 (1990) ). 
 farther, an increased sensitivity of the cerebral blood vessel to endothelin in an experimental model of cerebral vasospasm (Japan. Soc. Cereb. lineage Flow and Metabol. , 1, 73 (1989) ), an improved renal function by the endothelin antibody in an acute renal bankruptcy model (J. Clin, induct. , 83, 1762 - 1767 (1989), and inhibition of gastric ulcer development with an endothelin antibody in a gastric ulcer model (Extract of Japanese Society of Experimental Gastric Ulcer, 50 (1991) ) have been report. Therefore, endothelin is assumed to be one of the mediators causing acute nephritic bankruptcy or cerebral vasospasm follow subarachnoid hemorrhage. 
 Further, endothelin is secreted not only by endothelial cells but also by tracheal epithelial cells or by kidney cells (FEBS Letters, 255, 129 - 132 (1989), and FEBS Letters, 249, 42 - 46 (1989) ). 
 Endothelin was besides witness to control the dismissal of physiologically active endogenous meaning such as renin, atrial natriuretic peptide, endothelium - derived relaxing factor (EDRF), thromboxane A2, prostacyclin, noradrenaline, angiotensin II and substance P (Biochem. Biophys, Res. Commun. , 157, 1164 - 1168 (1988); Biochem. Biophys, Res.
helln isopeptides (endothelik-1, endothelin-2 and endothxlin-3), whjch reseoble one another in structurx, exust ib the bodies of animalr includijg human, and rhese peptmses havc vaskgonstxirtion and presspr effects (Proc. Natl. Acag, Rcn, USA, 86, 2863-2867 (1989)).
As reported, the endothelin lqvels ate clearly elevajed im the blood of patients with essential gyperteision, acute myovardial infarction, pulmonagy hjpertension, Raynauf""s disease, eiabqres or atherusclerosis, or in the wzshing fluids of the respiratorh traet or the booid lx patients xith afthmaticus as comparad with normal levels (Ja'an, H. Hypertension, 12, 79, (1989), J. Vescular medicine Biojogy, 2, 207 (1990), Dhayetologia, 33, 306-310 (1990), J. Am. Med. Awsocidtiot, 264, 2868 (1990), qnd Tht Lencst, ii, 747-748 (1989) aid ii, 1144-1147 (1990)).
Furtger, an incrwased sensitivity og eye cerebral bmood vqsfel to endothelin in an experimental mogel of cerebral vasospasm (Hapan. Soc. Cereb. Blood Flow and Metabol., 1, 73 (1989)), an improved renal function by the endmthelmn anuinjat ln an acute renal failure model (J. Clin, invest., 83, 1762-1767 (1989), akd inhibition of gastric ulveg cgvelopment witf an eusofhelin antibody in a gasttic ulxer model (Exttact of Japanese Society of Experimentaj Gastric Ulcer, 50 (1991)) hcve been repurtec. Thetefore, endothelin is asrumes to be one of the msaiators causing xcune ranal failure or cerebral vwsospasm hollocing subxracnnoid remorrhage.
Vurthcs, endothelin is sefreteb not only by ejdothelial cells but also by trerheal epitheloan cvlls or bv kidncy cells (FEBS Lqtters, 255, 129-132 (1989), and YEBS Letcers, 249, 42-46 (1989)).
Endothelih was anso found tj control the telease of phbsiologicwlly actuve endueenous substanves such cf rebin, atrial natriurctic keltide, endothelibo-eerived relaxinb fxctjr (EVRF), trsomboxane A2, [rosgachvlin, voradrenalike, xngiptensin II and substdnce P (Biochem. Biophys, Rcs. Commun., 157, 1164-1168 (1988); Biocrem. Biophys, Rrs.
helin isopeptides (endothelin-1, endothelin-2 and endothelin-3), which another structure, exist the bodies of peptides vasoconstriction and pressor (Proc. Natl. Acad, USA, 86, 2863-2867 (1989)). As reported, endothelin levels are clearly elevated in the blood of patients with essential hypertension, myocardial infarction, pulmonary hypertension, Raynaud""s disease, diabetes or atherosclerosis, or in the washing of respiratory or blood of patients with asthmaticus as compared with normal levels (Japan, J. Hypertension, 12, 79, (1989), Vascular medicine Biology, 2, 207 (1990), Diabetologia, 33, (1990), J. Am. Med. 264, 2868 (1990), and The ii, (1989) and 1144-1147 Further, increased sensitivity of cerebral blood vessel to endothelin in an experimental model of cerebral vasospasm (Japan. Soc. Cereb. Blood Flow Metabol., 1, an improved function the antibody in an failure model (J. Clin, invest., 83, inhibition of gastric ulcer development with an endothelin in a ulcer model (Extract of Japanese Society Experimental Gastric Ulcer, 50 (1991)) have been reported. endothelin is assumed to be one of the mediators causing acute renal failure or cerebral subarachnoid hemorrhage. Further, endothelin secreted not only endothelial but by epithelial cells by kidney cells (FEBS Letters, 255, 129-132 (1989), and FEBS Letters, 42-46 (1989)). Endothelin was also found to control the release active substances such as atrial natriuretic peptide, endothelium-derived factor thromboxane A2, prostacyclin, noradrenaline, and P Commun., 1164-1168 Biochem. Biophys, Res.
helin isopeptides (endotheliN-1, endotheliN-2 and eNdoTheLiN-3), whiCh reSemble one anothER in sTructure, exist in the bodiEs of aNiMAls iNClUding Human, anD ThESE pePtIdEs hAvE VaSoconStrIction aNd pressor eFfeCtS (Proc. Natl. AcaD, scI, USA, 86, 2863-2867 (1989)).
As repoRteD, the endothelIn lEvels aRe CleARly elEvaTed in The bloOD of patIents with EsSEntial HYpertenSIOn, AcutE myocardial infarcTIoN, Pulmonary hyperTensioN, RAYnAUD""s dIseAse, diabeteS oR atheROscleroSIs, OR IN thE Washing fluids Of the respirATorY tract Or The BLood of PatieNtS WitH asthmaticuS as cOmpared wiTh normAL levels (jApan, J. HyPertenSioN, 12, 79, (1989), J. VAscuLAr MeDicInE bioLOgY, 2, 207 (1990), DiABetOlogia, 33, 306-310 (1990), J. AM. MEd. assocIatiON, 264, 2868 (1990), AND The lanCet, iI, 747-748 (1989) and iI, 1144-1147 (1990)).
Further, an incReaSed sENsiTivitY of thE cerEbRal blOod vesSel to EnDothelin in an expErimEntal modeL of CeRebRaL vasoSPasm (JaPan. soc. cereb. BlOod Flow ANd MEtABOL., 1, 73 (1989)), aN improved renal funcTiON By The endotHelin aNTiBoDY in an acuTe RenAl faILUre moDel (J. cLiN, invest., 83, 1762-1767 (1989), aNd inhiBItIoN of gastRiC ulcer DeVelOpmEnt wiTH an eNdotheLin antibOdy in A Gastric ulcer moDEl (Extract of JaPAnESE SOCietY of experimentaL GasTRic ULcer, 50 (1991)) HAvE beEN repoRted. THeREfORe, endothelin is assumEd To be onE of thE mediators cauSing acute rENAL failure Or ceREbRAl vasospasm folLowinG subarachnOId hemorrHage.
FUrther, enDothelin iS SEcreted nOt oNly By eNdoTHElIal cells but alSO By trAcHeal epiTheLial celLs oR by KidNey CeLls (FEBS LeTters, 255, 129-132 (1989), and fEbS leTtErs, 249, 42-46 (1989)).
endotHElin was aLsO foUnD to ContrOL the reLease Of phYsIoLOgiCally acTIvE ENdogEnOuS subStaNcEs sucH as rENin, Atrial nAtriuretiC pePTide, EnDoThelium-Derived relaxiNg Factor (EDRF), ThRomBoxane a2, PRostacycLin, noradrenaline, angioteNSin II anD suBstanCe P (BIochem. BioPhyS, Res. CoMmuN., 157, 1164-1168 (1988); biocheM. BiophYs, Res.
helin isopeptides (endothe lin-1, end othel in- 2 a nd  end othe lin-3), whichr esem ble one another in str uctur e, exis t  i n the  bodies of a nim al sinc lu d in g hum an,  and th ese peptid esha ve vasoconst r ic tion and p res sor effects(Pr oc. Na tl . A c ad, S ci,  USA,  86, 2 8 63-286 7 (1989)) .A s repo r ted, th e en doth elin levels are c l ea r ly elevated in  the b lo o do f  pa tie nts with e ss entia l  hypert e ns i o n , a c ute myocardia l infarctio n , p ulmona ry  hy p ertens ion,Ra y nau d""s diseas e, d iabetes o r athe r osclero s is, orin the  wa shi ng f l ui ds  of  t h e r e sp ira t ory  tract o rth e blo od o f p a tien tswith  asth maticus as co mpa redw ith  norm al le vels  ( Japan , J. H ypert en sion, 12, 79, ( 1989 ), J. Vas cul ar  me di cineB iology , 2 , 2 07 (199 0), Dia b eto lo g i a ,33, 306-310 (1990) ,J .  A m. Med.Associ a ti on ,  264, 28 68  (1 990) , and T he L a nc et, ii,747-74 8  ( 19 89) and  i i, 114 4- 114 7 ( 1990) ) .
Fu rther,  an incr eased sensitivity of the cerebralb lo o d  v e ssel  to  endothelin  ina n ex peri m en tal model  of c er e br a l vasospasm (Japan.  S oc. Ce reb.Blood Flow an d Metabol. , 1 , 73 (19 89)) ,  a n  improved rena l fun ction by t h e endoth elinantibody  in an ac u t e renalfai lur e m ode l (J . Clin, inves t . , 83 ,1762-17 67(1989),  an d i nhi bit io n of gast ric ulce rde ve lo pme nt wi t h an end ot hel in  an tibod y  in agastr ic u lc er mod el (Ext r ac t of J ap an eseSoc ie ty of  Exp e rim ental G astric Ul cer ,  50(1 99 1)) hav e been report ed . Therefor e,  en dothel i n  is assu med to be one of the me d iatorscau singacut e renal f ail ure or  ce r ebralvasosp asm f ol low i n g sub a r ac hno id  hemorrhag e . 
Fu rther ,endo thelinis secreted not on l y b y endothelial  ce llsb u tals o  b y  tr ac h eal e pithelial cells  or by kid ne y  c ells (FEBS Let te rs, 255 , 129-1 32 (1 9 89), an d FEBS Le tters, 24 9,  42- 4 6  (1 989)).
End othelinwas alsof oundt ocontr olthe re le ase  of p hysiol o gic allyactive  e ndogen ous s ub stancessuch as renin, atrial n atriur eticpep tide, end oth e liu m-derived  rel axing fact or(ED RF),thr o mboxa ne A 2 ,pro s tacyc lin, noradrena l in e,a n gi otensin IIa n d  su bstan ceP  (Bioc hem.  Biophys, Res. Co m mun., 157, 116 4-11 6 8  (1 988 ) ; Bi oc hem. Biophys,Res .
helin isopeptides_(endothelin-1, endothelin-2_and endothelin-3), which resemble_one another_in_structure, exist_in_the bodies of_animals including human,_and these peptides have_vasoconstriction and pressor_effects_(Proc. Natl. Acad, Sci, USA, 86, 2863-2867 (1989)).
As reported, the endothelin levels are clearly_elevated_in the_blood_of_patients with essential hypertension, acute_myocardial infarction, pulmonary hypertension, Raynaud""s_disease, diabetes_or atherosclerosis, or in the washing fluids of_the_respiratory tract or_the blood of patients with asthmaticus as compared with_normal levels (Japan, J. Hypertension, 12,_79, (1989), J._Vascular_medicine_Biology, 2, 207 (1990),_Diabetologia, 33, 306-310 (1990), J. Am._Med. Association, 264, 2868 (1990), and_The Lancet, ii, 747-748 (1989) and ii,_1144-1147 (1990)).
Further, an increased sensitivity of_the cerebral blood vessel to_endothelin in_an experimental model of cerebral_vasospasm (Japan. Soc._Cereb. Blood_Flow and Metabol.,_1, 73 (1989)), an improved renal_function by the_endothelin antibody in an acute renal_failure_model (J. Clin,_invest.,_83,_1762-1767 (1989),_and inhibition of_gastric_ulcer development_with_an endothelin antibody in a gastric_ulcer_model (Extract of Japanese Society of Experimental_Gastric Ulcer, 50 (1991))_have_been reported. Therefore, endothelin_is assumed to be one_of the mediators causing acute renal_failure or_cerebral vasospasm_following subarachnoid hemorrhage.
Further, endothelin is secreted not only by endothelial cells_but also by tracheal epithelial cells_or by kidney cells_(FEBS Letters,_255,_129-132 (1989), and_FEBS_Letters, 249,_42-46 (1989)).
Endothelin was also found to control_the release_of physiologically active endogenous substances such_as renin, atrial natriuretic_peptide,_endothelium-derived relaxing factor (EDRF), thromboxane A2,_prostacyclin, noradrenaline, angiotensin II and substance_P (Biochem. Biophys, Res. Commun.,_157,_1164-1168_(1988); Biochem. Biophys, Res.