- Email: [email protected]
Effects of 17β-estradiol on isolated arteries
170A
AJH-APRIL 1999-VOL. 12, NO. 4, PART 2
ASH XIV ABSTRACTS
B005
B006
INCREASED ctv[33 INTEGRINS IN MESENTERIC RESISTANCE ARTERIES FROM SHR: EFFECT OF ANTIHYPERTENSIVE THERAPY. H.D. Intengan, G. Thibault and E.L. Schiffrin" Clinical Research Institute of Montreal, Montreal, Quebec, Canada. The structure and mechanical properties (stiffness) of mesenteric resistance arteries may be altered in spontaneously hypertensive rats (SHR). We have reported that ctv133 integrins are upregulated in SHR mesenteric arteries as compared with normotensive WKY. We tested the hypothesis that antihypertensive therapy, specifically that which has been shown to regress vascular structure and mechanical abnormalities, may also influence the integrin profile in these vessels. Ten week old SHR were treated for 10 weeks with irbesartan (50 mg/kg/d) or fosinopril (10-30 mg/kg/d) and compared to normotensive WKY and untreated SHR. Protein (10 lag), extracted from whole ruesenteric arterial beds, was incubated with t2~I-echistatin (200,000 cpm), an RGD-containing disintegrin isolated from the venom of E. carinatus. Proteins were separated by 6% SDS-PAGE, followed by autoradiography. Two bands were detected with sizes of approximately 220 and 180 KDa, which correspond in size to ~5131 and ctv133 integrins, respectively. In SHR, ~tvJ33 integrins were increased to 135+_12% (p<0.05) of WKY levels. Fosinopril significantly attenuated this increase in ~tvJ33 levels to 74+_13% (p<0.05), and a trend towards a decrease was also seen with irbesartan (125+_24%). Thus, integrin receptors may play a role in the remodeling or mechanical changes of resistance arteries in SHR. The normalization of integrin profile in SHR may be a mechanism by which vascular abnormalities are regressed by anti-hypertensive therapy.
Key Words:
integrins, resistance arteries, irbesartan, fosinopril
EFFECTS OF FLUVASTATIN TREATMENT ON STRUCTURE AND FUNCTION
OF
RESISTANT
VESSELS
IN
SPONTANEOUSLY
Liangdi XIE , Zhihong LIN , Kegui WU,
HYPERTENSIVE RATS
Huajun WANG , Changsheng XU Hypertension Division, First Affiliated Hospital, Fujian MedicalCollege, Fuzhou, ER.CHINA. This study was to evaluate the effects of fluvastatin on the structure and function of resistant vessels in spontaneously hypertensive rats(SHRs). Male SHRs at 8 wks were given fluvastatin (SHRn.) 20 mg.kgtday~ by garage, and decapitated at 16 wks
after SBP and BW
measured. Wall-to-lumen area ratios (W/L) of aorta and mesenteric arteries (3rd branch) were assessed. Vascular reactivity to sodium nitroprusside (SNP) and NE was studied with rings of aorta and mesenteric arteries. After 8 wks treatment, SBP was significantly lower in SHRn, than in untreated SHR ( 191 + 13 vs 213 ± g mmHg, P
EC50 of relaxation response was much lower
significant, than that of untreated SHR (0.02 vs 0.04nmol "L-'. P>0.05). Both aortic and mesenteric rings from SHR~ exhibited depressed vasoconstriction response to NE as compared with untreated SHR. EC50 of vasoconstriction response in rings derived from SHRa. was higher than that of controls (aorta: 0.20 vs 0.02nmol • L-', P<0.05; mesentric: 1.46 vs 0.72nmol -L% P<0.05). These results indicated that fluvastutin enhanced the sensitivity to vasodilator, depressed t h e sensitivity to vasoconstrictor, and attenuated the hypertrophy of resistant artery during the development of hypertension in SHR. Key Words: fluvastatin; inbred SHR; resistant vessels;
B007 ENHANCED VASCULAR RESPONSE T O COLD PRESSOR TEST IS ASSOCIATED W I T H A POSITIVE F A M I L Y HISTORY OF HYPERTENSION. RP B o c h m ~ n , C Pl~mita, U Rcutsr Dept. of l~ysiol., Techn Univ. of Dresdm, Germany In a previous study w e have shown that in normutmsive subjects (N) and h y p ~ t m s i v e patients (H) the local blood pressure 0BP) of the digital armries and their compliance under cold pressor test (CPT) is significantly increased, respectively decreased. It is known that in the pathogmesis of hypertension exists a strong hereditary component. Aim: to detm'mine the influence of the family history of hypertension cm the reaction oflBP and the arterial compliance to CPT. Methods: The response to CPT (left hand into ice water for 1 mint w a s studied in 47 healthy subjects (120~9/71~6 ram Fig bradaial BP) and 46 mild hypertensive patients (1425:12/85:1:8 m m Fig • brachial BP) by comparing the last 15 s tmdor c F r to pretest. We used impedance plethysmography and a finger BP measuring device (FINAPRES) to determine beat-to-beat the IBP and the aaerial compliance from neighbour~ frog, s of the fight hand. We defined subgroups comprising individuals without parental hypertension (FO) and with both parents affected by hypertension (F2). R~ults: test - vrotest diiT~once F0 F2 systolic IBP (nun I"Is) in N: 9"J:l I 22+14 # in H: -4+92 17+10 # compliance in N: -0.8+1.1 -0.8~0.4 (pl/mm I-lg/lOO ml tissue) H: -0. l:L-O.9 -I.0:L-0.7 # (#: F2 eomparodto F0, with p
hypertension
B008 EFFECTS OF 17 I3-ESTRADIOL ON ISOLATED ARTERIES. M. CHU. X.D.LI. Dept. Phan~acology, Shanghai Medical, Universi~', Shanghai, China The lower incidence of ischermc heart disease in premcnopausal woman than in men is supposed to be caused by a protectiveactionof estradiols.The cardiovascularprotectiveactaon of eslrogen is reported to be mediated eitherby a directeffecton the vessel wall or by an indirecteffect on lipoproteinmetabolism. Tileaim of thisstudy"was to measure the effects of 17[3-estradiol (E2) on pig basilar arteries, l~ne Rngs were obtained tight after "Maughtcr.Thezings were suspended in organ baths for isomemc tension measugnnent. E2 110s, 10": ~, I0"5, 10" 5 M } produced concentration - dependent vasorelaxation on the m~xtmum contraction induced by KCI (40 raM/in artery nngs dC~0 was 10"~zmol.L% as shown in figure 1. After incubation with E, (10 k|0"2M ), the phasic eon~ction induced by KCI (40 raM) was inhibited in a concenlra~an-dependant manner (IC~0was 10"~~mol.Ll ), as shown in figure2; while #he concentration-effectCLLrVegenerated by 5-HT was also inlu'bited(pD; was 4.5,'7),as shown in ~ 3. In our recent study on molated human renal arteries, it seems that a concentration-effectcurve ~)J'uecd by N E was also inldlmted niter incubation with E2 ~/0-5,10"M) O~..r re:.v:Jts ~-~ggests that E2 has vt~odilatory effect on isffiared a,~,:~:';es
'
4.
.
.
.
,.
! :i; L
-6,S-5.5 4.5-3.5 d.2lE2ymol.1
-5.5 -5 -4.5 -4 -LgJF.2]/mo~l
.
.-~""
-85 -75 -~,5 -5,5 -45 .Lg(5-HT]/mog1
FiB I RelL~am affect of E2 Fi~ 2 IubJbltow effectof E2 Fi$ 3 Eff~¢~ orE2 on .~-HT oa KCI.,-iI~IucKI cO¢~tiOa Oa KC[,-iudl~ed c~lmtchoa ¢ o ~ ¢ ¢ n a , l ~ o a - ~
tu-'S); .*,q:~cO.OOl.v~tc,.~t;"P.O.OS.~PcO.OOI, coea'mction(1.-6); 'qP'
v t'~*SU~co,are[
Key Words: 17[~-ellzadiol; i s o ] ~ t Key Words: local blood pressure, arterial corapliance, digital artery, family history of hypertension. Granted by BMBF-Projela ,,Atherogenese"
in
SHRn. than in controls (4.9 × 10-3vs 0.19nmol • L~ , P<0.05 ) , while EC50 of mesenteric artery rings from SHRn, was lower, not statistically
'~qp<0.01 .Pc0.001 .vermin
control
AJH-APRIL 1999-VOL. 12, NO. 4, PART 2
ASH XIV ABSTRACTS
B005
B006
INCREASED ctv[33 INTEGRINS IN MESENTERIC RESISTANCE ARTERIES FROM SHR: EFFECT OF ANTIHYPERTENSIVE THERAPY. H.D. Intengan, G. Thibault and E.L. Schiffrin" Clinical Research Institute of Montreal, Montreal, Quebec, Canada. The structure and mechanical properties (stiffness) of mesenteric resistance arteries may be altered in spontaneously hypertensive rats (SHR). We have reported that ctv133 integrins are upregulated in SHR mesenteric arteries as compared with normotensive WKY. We tested the hypothesis that antihypertensive therapy, specifically that which has been shown to regress vascular structure and mechanical abnormalities, may also influence the integrin profile in these vessels. Ten week old SHR were treated for 10 weeks with irbesartan (50 mg/kg/d) or fosinopril (10-30 mg/kg/d) and compared to normotensive WKY and untreated SHR. Protein (10 lag), extracted from whole ruesenteric arterial beds, was incubated with t2~I-echistatin (200,000 cpm), an RGD-containing disintegrin isolated from the venom of E. carinatus. Proteins were separated by 6% SDS-PAGE, followed by autoradiography. Two bands were detected with sizes of approximately 220 and 180 KDa, which correspond in size to ~5131 and ctv133 integrins, respectively. In SHR, ~tvJ33 integrins were increased to 135+_12% (p<0.05) of WKY levels. Fosinopril significantly attenuated this increase in ~tvJ33 levels to 74+_13% (p<0.05), and a trend towards a decrease was also seen with irbesartan (125+_24%). Thus, integrin receptors may play a role in the remodeling or mechanical changes of resistance arteries in SHR. The normalization of integrin profile in SHR may be a mechanism by which vascular abnormalities are regressed by anti-hypertensive therapy.
Key Words:
integrins, resistance arteries, irbesartan, fosinopril
EFFECTS OF FLUVASTATIN TREATMENT ON STRUCTURE AND FUNCTION
OF
RESISTANT
VESSELS
IN
SPONTANEOUSLY
Liangdi XIE , Zhihong LIN , Kegui WU,
HYPERTENSIVE RATS
Huajun WANG , Changsheng XU Hypertension Division, First Affiliated Hospital, Fujian MedicalCollege, Fuzhou, ER.CHINA. This study was to evaluate the effects of fluvastatin on the structure and function of resistant vessels in spontaneously hypertensive rats(SHRs). Male SHRs at 8 wks were given fluvastatin (SHRn.) 20 mg.kgtday~ by garage, and decapitated at 16 wks
after SBP and BW
measured. Wall-to-lumen area ratios (W/L) of aorta and mesenteric arteries (3rd branch) were assessed. Vascular reactivity to sodium nitroprusside (SNP) and NE was studied with rings of aorta and mesenteric arteries. After 8 wks treatment, SBP was significantly lower in SHRn, than in untreated SHR ( 191 + 13 vs 213 ± g mmHg, P
EC50 of relaxation response was much lower
significant, than that of untreated SHR (0.02 vs 0.04nmol "L-'. P>0.05). Both aortic and mesenteric rings from SHR~ exhibited depressed vasoconstriction response to NE as compared with untreated SHR. EC50 of vasoconstriction response in rings derived from SHRa. was higher than that of controls (aorta: 0.20 vs 0.02nmol • L-', P<0.05; mesentric: 1.46 vs 0.72nmol -L% P<0.05). These results indicated that fluvastutin enhanced the sensitivity to vasodilator, depressed t h e sensitivity to vasoconstrictor, and attenuated the hypertrophy of resistant artery during the development of hypertension in SHR. Key Words: fluvastatin; inbred SHR; resistant vessels;
B007 ENHANCED VASCULAR RESPONSE T O COLD PRESSOR TEST IS ASSOCIATED W I T H A POSITIVE F A M I L Y HISTORY OF HYPERTENSION. RP B o c h m ~ n , C Pl~mita, U Rcutsr Dept. of l~ysiol., Techn Univ. of Dresdm, Germany In a previous study w e have shown that in normutmsive subjects (N) and h y p ~ t m s i v e patients (H) the local blood pressure 0BP) of the digital armries and their compliance under cold pressor test (CPT) is significantly increased, respectively decreased. It is known that in the pathogmesis of hypertension exists a strong hereditary component. Aim: to detm'mine the influence of the family history of hypertension cm the reaction oflBP and the arterial compliance to CPT. Methods: The response to CPT (left hand into ice water for 1 mint w a s studied in 47 healthy subjects (120~9/71~6 ram Fig bradaial BP) and 46 mild hypertensive patients (1425:12/85:1:8 m m Fig • brachial BP) by comparing the last 15 s tmdor c F r to pretest. We used impedance plethysmography and a finger BP measuring device (FINAPRES) to determine beat-to-beat the IBP and the aaerial compliance from neighbour~ frog, s of the fight hand. We defined subgroups comprising individuals without parental hypertension (FO) and with both parents affected by hypertension (F2). R~ults: test - vrotest diiT~once F0 F2 systolic IBP (nun I"Is) in N: 9"J:l I 22+14 # in H: -4+92 17+10 # compliance in N: -0.8+1.1 -0.8~0.4 (pl/mm I-lg/lOO ml tissue) H: -0. l:L-O.9 -I.0:L-0.7 # (#: F2 eomparodto F0, with p
hypertension
B008 EFFECTS OF 17 I3-ESTRADIOL ON ISOLATED ARTERIES. M. CHU. X.D.LI. Dept. Phan~acology, Shanghai Medical, Universi~', Shanghai, China The lower incidence of ischermc heart disease in premcnopausal woman than in men is supposed to be caused by a protectiveactionof estradiols.The cardiovascularprotectiveactaon of eslrogen is reported to be mediated eitherby a directeffecton the vessel wall or by an indirecteffect on lipoproteinmetabolism. Tileaim of thisstudy"was to measure the effects of 17[3-estradiol (E2) on pig basilar arteries, l~ne Rngs were obtained tight after "Maughtcr.Thezings were suspended in organ baths for isomemc tension measugnnent. E2 110s, 10": ~, I0"5, 10" 5 M } produced concentration - dependent vasorelaxation on the m~xtmum contraction induced by KCI (40 raM/in artery nngs dC~0 was 10"~zmol.L% as shown in figure 1. After incubation with E, (10 k|0"2M ), the phasic eon~ction induced by KCI (40 raM) was inhibited in a concenlra~an-dependant manner (IC~0was 10"~~mol.Ll ), as shown in figure2; while #he concentration-effectCLLrVegenerated by 5-HT was also inlu'bited(pD; was 4.5,'7),as shown in ~ 3. In our recent study on molated human renal arteries, it seems that a concentration-effectcurve ~)J'uecd by N E was also inldlmted niter incubation with E2 ~/0-5,10"M) O~..r re:.v:Jts ~-~ggests that E2 has vt~odilatory effect on isffiared a,~,:~:';es
'
4.
.
.
.
,.
! :i; L
-6,S-5.5 4.5-3.5 d.2lE2ymol.1
-5.5 -5 -4.5 -4 -LgJF.2]/mo~l
.
.-~""
-85 -75 -~,5 -5,5 -45 .Lg(5-HT]/mog1
FiB I RelL~am affect of E2 Fi~ 2 IubJbltow effectof E2 Fi$ 3 Eff~¢~ orE2 on .~-HT oa KCI.,-iI~IucKI cO¢~tiOa Oa KC[,-iudl~ed c~lmtchoa ¢ o ~ ¢ ¢ n a , l ~ o a - ~
tu-'S); .*,q:~cO.OOl.v~tc,.~t;"P.O.OS.~PcO.OOI, coea'mction(1.-6); 'qP'
v t'~*SU~co,are[
Key Words: 17[~-ellzadiol; i s o ] ~ t Key Words: local blood pressure, arterial corapliance, digital artery, family history of hypertension. Granted by BMBF-Projela ,,Atherogenese"
in
SHRn. than in controls (4.9 × 10-3vs 0.19nmol • L~ , P<0.05 ) , while EC50 of mesenteric artery rings from SHRn, was lower, not statistically
'~qp<0.01 .Pc0.001 .vermin
control