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ADDIN RW.BIBTHE HYPERTENSION OF CUSHINGS SYNDROME: CONTROVERSIES IN THE PATHOPHYSIOLOGY AND FOCUS ON CARDIOVASCULAR COMPLICATIONS.
Supplemental Tables 1S
Supplemental Tables 2S
Supplemental References
Table 1S. Original studies investigating the mechanisms involved in the pathogenesis of hypertension induced by glucocorticoid excess.
Human StudiesAnimal StudiesReferenceReferenceRENIN ANGIOTENSIN ! A n g i o t e n s i n o g e n w i t h : ! A n g i o t e n s i n o g e n w i t h : S Y S T E M ( R A S ) N o r m a l p l a s m a r e n i n a c t i v i t y ( P R A ) a n d p l a s m a r e n i n c o n c e n t r a t i o n i n C S
S u b j e c t s : 1 2 u n t r e a t e d C S ( 5 M , 7 F , a g e 1 9 - 6 5 y r ) v s . 6 N T ( 3 M , 3 F , m e a n a g e 3 1 y r s )
S u b j e c t s : 9 C S v s . 1 0 P A , 1 0 RVH, 10 EH, 10 NT
Subjects: 8 CS
Subjects: 12 CS
ADDIN REFMGR.CITE Saruta198645Multiple factors contribute to the pathogenesis of hypertension in Cushing's syndromeJournal45Multiple factors contribute to the pathogenesis of hypertension in Cushing's syndromeSaruta,T.Suzuki,H.Handa,M.Igarashi,Y.Kondo,K.Senba,S.1986/2AdenomaAdrenal Gland NeoplasmsAdultAgedAldosteroneAngiotensin IIAngiotensinogenbloodBlood PressureCaptoprilcomplicationsCushing SyndromeDinoprostoneetiologyFemaleHumansHydrocortisoneHypertensionKallikreinsMalemetabolismMiddle AgedNorepinephrinepharmacologyProstaglandins EReninRenin-Angiotensin SystemurineNot in File275279J.Clin.Endocrinol.Metab622PM:3510223J.Clin.Endocrinol.Metab11, ADDIN REFMGR.CITE ADDIN EN.CITE.DATA 2, ADDIN REFMGR.CITE Krakoff197558Pathogenesis of hypertension in Cushing's syndromeJournal58Pathogenesis of hypertension in Cushing's syndromeKrakoff,L.Nicolis,G.Amsel,B.1975/217-KetosteroidsAdenomaAdultAngiotensin IIbiosynthesisbloodcomplicationsCushing SyndromeDietetiologyFemaleHumansHydrocortisoneHydroxysteroidsHypertensionMalemetabolismMiddle AgedPotassiumReninsecretionSodiumSodium ChlorideurineNot in File216220Am.J.Med.582PM:1115068Am.J.Med.13, ADDIN REFMGR.CITE Tenschert1985124Pathogenetic aspects of hypertension in Cushing's syndromeJournal124Pathogenetic aspects of hypertension in Cushing's syndromeTenschert,W.Baumgart,P.Greminger,P.Vetter,W.Vetter,H.1985AdolescentAdultAgedAldosteroneAngiotensinogenbloodBlood PressureCatecholaminesChildCircadian RhythmcomplicationsCushing SyndromeetiologyFemaleHumansHydrocortisoneHypertensionMaleMiddle AgedPotassiumReninRenin-Angiotensin SystemsecretionurineNot in File8490Cardiology72 Suppl 1PM:3902234Cardiology14
Normal plasma renin activity (PRA) and plasma renin concentration in vivo in
Male rats treated with 3 mg/Kg/day of DEX, or Male dogs treated with 0.5 mg/kg/day of DEX
ADDIN REFMGR.CITE Saruta199640Mechanism of glucocorticoid-induced hypertensionJournal40Mechanism of glucocorticoid-induced hypertensionSaruta,T.1996/3Angiotensin IIAnimalschemically inducedCushing SyndromeGlucocorticoidsHumansHypertensionNitric OxideNorepinephrinephysiologyphysiopathologyRatsRenintoxicityNot in File18Hypertens.Res.191Department of Internal Medicine, School of Medicine, Keio University, Tokyo, JapanPM:8829818Hypertens.Res.15Suppressed plasma renin activity (PRA) and plasma renin concentration in vivo
Subjects: Exogenous CS: 6 NT treated with ACTH 0.5 mg i.m. 12 hr.ly or cortisol 50 mg 6 hr.ly for 5 days
Subjects: 14 CS (8 CD, 1 adrenal adenoma, 5 adrenal carcinomas, 4 M, 11 F) vs 14 NT vs. and 10 EH
Subjects: Exogenous CS: 5 NT, 2 EH treated with cortisol (6 mg/h in F, 8 mg/h in M) for 5 days ADDIN REFMGR.CITE Connell198753Effects of ACTH and cortisol administration on blood pressure, electrolyte metabolism, atrial natriuretic peptide and renal function in normal manJournal53Effects of ACTH and cortisol administration on blood pressure, electrolyte metabolism, atrial natriuretic peptide and renal function in normal manConnell,J.M.Whitworth,J.A.Davies,D.L.Lever,A.F.Richards,A.M.Fraser,R.1987/8Adrenocorticotropic HormoneAdultAnimalsAtrial Natriuretic FactorbloodBlood Pressuredrug effectsElectrolytesExtracellular SpaceGlucocorticoidsHemodynamicsHumansHydrocortisoneKidneyMalemetabolismMiddle AgedNatriuresispharmacologyPlasma VolumePotassiumRenin-Angiotensin SystemSodiumVascular ResistanceNot in File425433J.Hypertens.54MRC Blood Pressure Unit, Western Infirmary, Glasgow, ScotlandPM:2822795J.Hypertens.16, ADDIN REFMGR.CITE Ehlers198757Elevated urinary 19-Nor-deoxycorticosterone glucuronide in Cushing's syndromeJournal57Elevated urinary 19-Nor-deoxycorticosterone glucuronide in Cushing's syndromeEhlers,M.E.Griffing,G.T.Wilson,T.E.Melby,J.C.1987/5AdenomaAdrenal Cortex NeoplasmsAdultAgedAldosteroneanalogs & derivativesbloodCarcinomacomplicationsCushing SyndromeDesoxycorticosteroneetiologyFemaleHumansHydrocortisoneHypertensionMalemetabolismMiddle AgedMineralocorticoidsPituitary NeoplasmsPotassiumurineNot in File926930J.Clin.Endocrinol.Metab645PM:3558730J.Clin.Endocrinol.Metab17, ADDIN REFMGR.CITE Whitworth198454Blood pressure and metabolic effects of cortisol and deoxycorticosterone in manJournal54Blood pressure and metabolic effects of cortisol and deoxycorticosterone in manWhitworth,J.A.Saines,D.Scoggins,B.A.1984AdolescentAdultbloodBlood PressureBody WeightDesoxycorticosteroneDiastoledrug effectsFemaleHumansHydrocortisoneHypertensionInfusions,ParenteralMalemetabolismMiddle AgedpharmacologyphysiopathologyReninSystoleTime FactorsurineNot in File795809Clin.Exp.Hypertens.A64PM:6723088Clin.Exp.Hypertens.A18 ! D B P i n r e s p o n s e t o p e r i p h e r a l a d m i n i s t r a t i o n o f A n g I I
I n t r a v e n o u s A N G I I i n f u s i o n o f 1 t o 6 n g / k g p e r m i n . ( 1 0 m i n ) S u b j e c t s : 1 2 u n t r e a t e d C S ( 5 M , 7 F , a g e 1 9 - 6 5 y r ) v s . 6 N T ( 3 M , 3 F , m e a n a g e 3 1 y r s )
I n t r a v e n o u s A N G I I i n f u s i o n o f 0 . 1 - 3 . 0 n g /kg-1/min-1) Subjects: 9 CS vs. 10 PA, 10 RVH, 10 EH, 10 NT ADDIN REFMGR.CITE Saruta198645Multiple factors contribute to the pathogenesis of hypertension in Cushing's syndromeJournal45Multiple factors contribute to the pathogenesis of hypertension in Cushing's syndromeSaruta,T.Suzuki,H.Handa,M.Igarashi,Y.Kondo,K.Senba,S.1986/2AdenomaAdrenal Gland NeoplasmsAdultAgedAldosteroneAngiotensin IIAngiotensinogenbloodBlood PressureCaptoprilcomplicationsCushing SyndromeDinoprostoneetiologyFemaleHumansHydrocortisoneHypertensionKallikreinsMalemetabolismMiddle AgedNorepinephrinepharmacologyProstaglandins EReninRenin-Angiotensin SystemurineNot in File275279J.Clin.Endocrinol.Metab622PM:3510223J.Clin.Endocrinol.Metab11, ADDIN REFMGR.CITE ADDIN EN.CITE.DATA 2
! D B P i n r e s p o n s e t o p e r i p h e r a l a d m i n i s t r a t i o n o f A n g I I
I n r a t s t r e a t e d w i t h D E X i n v i v o
A D D I N R E F M G R . C I T E A D D I N E N . C I T E . D A T A 5 , 9 , 1 0 ! A T - I I 1 A r e c e p t o r i n b l o o d c e l l s
! A T - I I 1 A e x p r e s s i o n b e f o r e a d r e n a l e c t o m y ,
! A T - I I 1 A a f t e r a d r e n a l e c t o m y
S u b j e c t s : 7 C S ( a d r e n a l a d e n o m a ) v s 7 N T w i t h r e n a l c e l l c a r c i n o m a
A D D I N R E F M G R . C I T E A D D I N E N . C I T E . D A T A 1 1 ! A T - I I 1 A r e c e p t o r i n p e r i p h e r a l v a s c u l a t u r e a n d t h e c e n t r a l n e r v o u s s y s t e m
I n r a t s t r e a t e d w i t h D E X A D D I N R E F M G R . C I T E A D D I N E N . C I T E . D A T A 5 , 1 2 , 1 3 M I N E R A L C O R T I C O I D 1 1 - H S D 2 s a t u r a t i o n E n h a n c e d H y p e r t e n s i n o g e n i c i t y o f A C T I V I T Y ! T H F + a l l o T H F / T H E r a t i o i n C S
! U F F / U F E r a t i o i n C S
S u b j e c t s : 2 2 C S ( 1 1 C D , 9 E A S , 2 a d r e n a l a d e n o m a s ; m e a n a g e 4 8 3 y r ; 6 M , 1 6 F ) v s . 1 3 NT (mean age 38 3yr; 3 M, 10 F) [5/22 CS were on antihypertensive medication: no spironolactone or ACE inhibitors] ADDIN REFMGR.CITE Stewart1995411 beta-Hydroxysteroid dehydrogenase activity in Cushing's syndrome: explaining the mineralocorticoid excess state of the ectopic adrenocorticotropin syndromeJournal411 beta-Hydroxysteroid dehydrogenase activity in Cushing's syndrome: explaining the mineralocorticoid excess state of the ectopic adrenocorticotropin syndromeStewart,P.M.Walker,B.R.Holder,G.O'Halloran,D.Shackleton,C.H.1995/1211-beta-Hydroxysteroid DehydrogenasesACTH Syndrome,EctopicCushing SyndromeetiologyFemaleHumansHydrocortisoneHydroxysteroid DehydrogenasesHypertensionMalemetabolismMiddle AgedMineralocorticoidsTetrahydrocortisolTetrahydrocortisoneNot in File36173620J.Clin.Endocrinol.Metab8012Department of Medicine, Queen Elizabeth Hospital, Birmingham, United KingdomPM:8530609J.Clin.Endocrinol.Metab114
19-Nor-DOC infusion
10-25 mcg/day for 2 weeks in Adrenalectomized spontaneously hypertensive rats
ADDIN REFMGR.CITE Gorsline198561The hypertensinogenic activity of 19-nor-deoxycorticosterone in the adrenalectomized spontaneously hypertensive ratJournal61The hypertensinogenic activity of 19-nor-deoxycorticosterone in the adrenalectomized spontaneously hypertensive ratGorsline,J.Morris,D.J.1985/10Adrenalectomyanalogs & derivativesAnimalsbloodBlood PressureDesoxycorticosteronedrug effectsMalepharmacologyRatsRats,Inbred SHRReninNot in File535536J . S t e r o i d B i o c h e m . <