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p53 is not involved in the overexpression of bax protein in the left ventricle of SHR
AJH-APRIL
1999-VOL.
12, NO. 4, PART 2
ABNORMAL PROTHROMBOTIC FACTORS AND ENDOTHELIAL DYSFUNCTION IN ISOLATED SYSTOLIC HYPERTENSION: IMPLICATIONS FOR THROMBOGENESIS AND ATHBRGGENESIS. University Department GYH Lip, AD Blann. AF Jones. and DG. of Medicine, City Hospital, Birmingham, England. Whilst the blood vessels are exposed to high pressures in hypertension, the main complications of hypertension (stroke ind myocardial infarction) are paradoxically thrombotic rather than investigate this further, we mcaslaed haemorrhagic. To haemorheological factors (fibrinogen, haematocrit, plasma viscosity) wd markers of endothelial dysfunction (van Willebrand factor. vWf). platelet activation (soluble P-selectm. sPse.1). thrombogenesis (Ddimer wd plasminogen activator inhibitor, PAI-I) and lipoprotein (a) (J&a), associated with thrombogensis and athemgenesis) in 23 patients (7 males; mean age 65.6 years) with isolated systolic hypertension [ISH, defined as systolic blood pressure @BP) >I@mmHg and diastolic blood pressure (DBP) <9OmmHg]. Results were compared lo 51 matched patients with essential hypertension (EH, >160/95mmHg: 24males) and 34 normorensive healthy controls (HC). p value ISH EH HC mean(s.d.) 198.5/l II.9 129.5/78.4
Key Words:
ORALS:
Hypertension
Mechanisms
IMPAIRED SYNTHESIS OF ELASTIN DURING FETAL AND INFANT LIFE AS A CAUSE OF RAISED ADULT BLOOD PRESSURE. CN Martvn, SE Greenwald and N Phillips. MRC Environmental Epidemiology Unit, Southampton University, Southampton, U.K. Epidemiological studies have shown that people whose birtbweigbt was low have higher blood pressures. But little is known about the underlying biological processes. We have suggested that, in fetuses whose growth is retarded, there is a reduction in the synthesis of elsstin during a critical period of arterial development. Because mature cross-linked elastin cannot be laid down in adult life, this permanently affects their mechanical properties. A deficiency in elastin results in a reduction in arterial compliance and leads to higher puke and mean blood pressures. Over a lifetime, the gradual loss of elastin that accompanies ageing and its replacement with collagen will tend to amplify the increase in blood pressure and might also predispose to left ventricular hypertrophy and vascular disease. We tested the hypothesis by measuring pulse wave velocity in a group (n=141) of 70 year old men and women whose hospital birth records had survived. People with higher pulse wave velocities, and therefore stiffer aortas, tended to have been lighter at birth. In a multiple regression analysis, after adjusting for sex, gestational age at birth and current blood pressure, pulse wave velocity decreased by 98% for each lb rise in birthweight @=0.03). The relation persists after adjustment for current blood pressure which suggests that reduced aortic elasticity was a primary event rather than simply a consequence of raised blood pressure. Key Words:
elastin, fetal growth, arterial compliance
Isolated systolic hypertension, Ihmmbogenesis. endothelial dysfuncoon
~53 IS NOT INVOLVED IN THE OVERBXPRESSION OF BAX PROTEIN IN THE LEFT VENTRICLE OF SHR. MA F-0, G Z&a, A Forttio, S Ravassa, B D’Lom, J Diea*. School of
Medicine,University of Navarra, Pamplona. Spain. We have previously reported an increased expression of the proapoptotic protein Bax, in association with an augmmted apoptasis in the lei? ventricle (LV) of adult SHR (Hypcrtcnsion 1998;82:280-286). Both alterations were corrcctcd in SHR Chronicaly treated with the AT, antagonist Loaarkm. The present study was designed to investigate whether the BAX mRNA is also increased and whether the expression of ~53, a BAX gene traosctiption factor, is augmented in the LV of SHR. In addition, the effects of Losartao in these parametas were also analyzed in treated SHR. The study was performed in the LV of 30 week-old normotensive Wistar-Kyoto rats (WKY. n=8), 30-week+ld untreated SHR (n=P), and 30 week-old SHR treated with Losartao during 14 weeks. BAX mItNA was assessed by Northern blotting, normalizing the values with the expression of the GAPDH gene. The presence of p53 and Bax proteins was determbxd by Western blotting Although Bax pro&n was increased (p
KeYWords: Apoptosis, Bax. left ventricle., ~53. SHR,
SUPPRESSION OF DEFECTIVE ALDGSTERONE BIOSYNTHESIS DURING STROKE PERMISSIVE DIET IN THE STROKE-PRONE SHR. B. GiPente, P.De Paolis, A. Porcellini, A.F. Mele, C. Savoia, R. Russo, R. Giliberti, I. Enea, S. Rubattn, D. Ganten”, M. Volpe’. Istituto Neurologico Mediterraneo Neuromed, Pozzilli (Is), and Dep. Exper. Med. and Path., Univ. La Sapienza, Rome, Italy; “MIX, Berlin, Germany. A dysregulation of the renin-angiotensin-aldosterone system has been previously described in the stroke-prone SHR (SHRsp) under a high salt, japanese style, diet (JD) and it has been related to the higher incidence of cerebrovascular events of this rat strain. To investigate the mechanisms underlying this hormonal abnormality, we studied aldosterone biosynthesis and production during JD in 6 week-old SHRsp and compared it with that observed in the stroke-resistant rat (SHRsr) under the same dietary treatment mantained for 4 weeks. In spite of comparable blood pressure levels, we observed a divergent aldosterone response in the two strains: from 442f56 to 739i126, ~4.05, in the SHRsp and from 357ti7 to 163ti1, ~~0.05, in the SHRsr. Consistently, the aldosterone syntbase expression was significantly increased in SHRsp and reduced in SHRsr, so that its mRNA levels were 5 fold higher in SHRsp vs SHRsr (p
Key Words:
Cerebmvascular handling
disease, aldostemne, Na’
7A
1999-VOL.
12, NO. 4, PART 2
ABNORMAL PROTHROMBOTIC FACTORS AND ENDOTHELIAL DYSFUNCTION IN ISOLATED SYSTOLIC HYPERTENSION: IMPLICATIONS FOR THROMBOGENESIS AND ATHBRGGENESIS. University Department GYH Lip, AD Blann. AF Jones. and DG. of Medicine, City Hospital, Birmingham, England. Whilst the blood vessels are exposed to high pressures in hypertension, the main complications of hypertension (stroke ind myocardial infarction) are paradoxically thrombotic rather than investigate this further, we mcaslaed haemorrhagic. To haemorheological factors (fibrinogen, haematocrit, plasma viscosity) wd markers of endothelial dysfunction (van Willebrand factor. vWf). platelet activation (soluble P-selectm. sPse.1). thrombogenesis (Ddimer wd plasminogen activator inhibitor, PAI-I) and lipoprotein (a) (J&a), associated with thrombogensis and athemgenesis) in 23 patients (7 males; mean age 65.6 years) with isolated systolic hypertension [ISH, defined as systolic blood pressure @BP) >I@mmHg and diastolic blood pressure (DBP) <9OmmHg]. Results were compared lo 51 matched patients with essential hypertension (EH, >160/95mmHg: 24males) and 34 normorensive healthy controls (HC). p value ISH EH HC mean(s.d.) 198.5/l II.9 129.5/78.4
Key Words:
ORALS:
Hypertension
Mechanisms
IMPAIRED SYNTHESIS OF ELASTIN DURING FETAL AND INFANT LIFE AS A CAUSE OF RAISED ADULT BLOOD PRESSURE. CN Martvn, SE Greenwald and N Phillips. MRC Environmental Epidemiology Unit, Southampton University, Southampton, U.K. Epidemiological studies have shown that people whose birtbweigbt was low have higher blood pressures. But little is known about the underlying biological processes. We have suggested that, in fetuses whose growth is retarded, there is a reduction in the synthesis of elsstin during a critical period of arterial development. Because mature cross-linked elastin cannot be laid down in adult life, this permanently affects their mechanical properties. A deficiency in elastin results in a reduction in arterial compliance and leads to higher puke and mean blood pressures. Over a lifetime, the gradual loss of elastin that accompanies ageing and its replacement with collagen will tend to amplify the increase in blood pressure and might also predispose to left ventricular hypertrophy and vascular disease. We tested the hypothesis by measuring pulse wave velocity in a group (n=141) of 70 year old men and women whose hospital birth records had survived. People with higher pulse wave velocities, and therefore stiffer aortas, tended to have been lighter at birth. In a multiple regression analysis, after adjusting for sex, gestational age at birth and current blood pressure, pulse wave velocity decreased by 98% for each lb rise in birthweight @=0.03). The relation persists after adjustment for current blood pressure which suggests that reduced aortic elasticity was a primary event rather than simply a consequence of raised blood pressure. Key Words:
elastin, fetal growth, arterial compliance
Isolated systolic hypertension, Ihmmbogenesis. endothelial dysfuncoon
~53 IS NOT INVOLVED IN THE OVERBXPRESSION OF BAX PROTEIN IN THE LEFT VENTRICLE OF SHR. MA F-0, G Z&a, A Forttio, S Ravassa, B D’Lom, J Diea*. School of
Medicine,University of Navarra, Pamplona. Spain. We have previously reported an increased expression of the proapoptotic protein Bax, in association with an augmmted apoptasis in the lei? ventricle (LV) of adult SHR (Hypcrtcnsion 1998;82:280-286). Both alterations were corrcctcd in SHR Chronicaly treated with the AT, antagonist Loaarkm. The present study was designed to investigate whether the BAX mRNA is also increased and whether the expression of ~53, a BAX gene traosctiption factor, is augmented in the LV of SHR. In addition, the effects of Losartao in these parametas were also analyzed in treated SHR. The study was performed in the LV of 30 week-old normotensive Wistar-Kyoto rats (WKY. n=8), 30-week+ld untreated SHR (n=P), and 30 week-old SHR treated with Losartao during 14 weeks. BAX mItNA was assessed by Northern blotting, normalizing the values with the expression of the GAPDH gene. The presence of p53 and Bax proteins was determbxd by Western blotting Although Bax pro&n was increased (p
KeYWords: Apoptosis, Bax. left ventricle., ~53. SHR,
SUPPRESSION OF DEFECTIVE ALDGSTERONE BIOSYNTHESIS DURING STROKE PERMISSIVE DIET IN THE STROKE-PRONE SHR. B. GiPente, P.De Paolis, A. Porcellini, A.F. Mele, C. Savoia, R. Russo, R. Giliberti, I. Enea, S. Rubattn, D. Ganten”, M. Volpe’. Istituto Neurologico Mediterraneo Neuromed, Pozzilli (Is), and Dep. Exper. Med. and Path., Univ. La Sapienza, Rome, Italy; “MIX, Berlin, Germany. A dysregulation of the renin-angiotensin-aldosterone system has been previously described in the stroke-prone SHR (SHRsp) under a high salt, japanese style, diet (JD) and it has been related to the higher incidence of cerebrovascular events of this rat strain. To investigate the mechanisms underlying this hormonal abnormality, we studied aldosterone biosynthesis and production during JD in 6 week-old SHRsp and compared it with that observed in the stroke-resistant rat (SHRsr) under the same dietary treatment mantained for 4 weeks. In spite of comparable blood pressure levels, we observed a divergent aldosterone response in the two strains: from 442f56 to 739i126, ~4.05, in the SHRsp and from 357ti7 to 163ti1, ~~0.05, in the SHRsr. Consistently, the aldosterone syntbase expression was significantly increased in SHRsp and reduced in SHRsr, so that its mRNA levels were 5 fold higher in SHRsp vs SHRsr (p
Key Words:
Cerebmvascular handling
disease, aldostemne, Na’
7A