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Biomedical subjects

J J Morton

Publications and source records attributed to J J Morton.

At least 37 records · Page 2Linked to original sources
PubMed1999

Inappropriately low plasma leptin concentration in the cachexia associated with chronic heart failure.

BACKGROUND: Cardiac cachexia is a syndrome of generalised wasting which caries a poor prognosis and is associated with raised plasma concentrations of tumour necrosis factor alpha (TNFalpha). TNFalpha increases secretion of leptin, a hormone which decreases food intake and increases energy expenditure. OBJECTIVE: To determine whether an inappropriate increase in plasma leptin concentration contributes to the cachexia of chronic heart failure. DESIGN: Retrospective case-control study. SETTING: Tertiary referral cardiology unit. PATIENTS: 110 human subjects comprising 29 cachectic chronic heart failure patients, 22 non-cachectic chronic heart failure patients, 33 patients with ischaemic heart disease but normal ventricular function, and 26 healthy controls. INTERVENTIONS: Measurement of: body fat content by skinfold thickness (cachectic males < 27%, females < 29%); plasma leptin, TNFalpha, and noradrenaline (norepinephrine); central haemodynamics in chronic heart failure patients at right heart catheterisation. MAIN OUTCOME MEASURES: Plasma leptin concentration corrected for body fat content, plasma TNFalpha and noradrenaline concentration, and central haemodynamics. RESULTS: Mean (SEM) plasma leptin concentrations were: 6.2 (0.6) ng/ml (cachectic heart failure), 16.9 (3.6) ng/ml (non-cachectic heart failure), 16.8 (3.0) ng/ml (ischaemic heart disease), and 18.3 (3.5) ng/ml (control) (p < 0.001 for cachectic heart failure v all other groups). Plasma leptin concentration remained significantly lower in the cachectic heart failure group even after correcting for body fat content and in spite of significantly increased TNFalpha concentrations. Thus plasma leptin was inappropriately low in cachectic chronic heart failure in the face of a recognised stimulus to its secretion. There was no significant correlation between plasma leptin, New York Heart Association class, ejection fraction, or any haemodynamic indices. CONCLUSIONS: Leptin does not contribute to the cachexia of chronic heart failure. One or more leptin suppressing mechanisms may operate in this syndrome-for example, the sympathetic nervous system.

Adipose Tissue↗
PubMed1999

Telemetry for cardiovascular monitoring in a pharmacological study: new approaches to data analysis.

Radio-telemetry systems offer the ability to measure blood pressure and heart rate in experimental models of hypertension without the stress artifacts induced by some other methods. We therefore aimed to develop improved, nonparametric regression methods for radio-telemetry data and to use these to assess the effects of pharmacological interventions on cardiac and vascular hypertrophy in the stroke-prone spontaneously hypertensive rat. One control group and 5 groups treated either with losartan (alone or in combination with NG-nitro-L-arginine methyl ester [ L-NAME]), perindopril (also alone or in combination with L-NAME), or hydralazine plus hydrochlorothiazide were monitored for 4 weeks. Cardiac hypertrophy was assessed by the left ventricle plus septum weight to body weight ratio and vascular hypertrophy by flow-cytometry analysis of vascular smooth muscle cell polyploidy. Hemodynamic series were split into trend and cyclic components by the seasonal and trend decomposition procedure based on Loess and compared between groups by Loess regression modeling. Systolic and diastolic blood pressures were reduced systematically by losartan and perindopril (P<10(-10)) but to a lesser extent by hydralazine plus hydrochlorothiazide (P<10(-8)), and diurnal variation was reduced in the latter group (P<10(-6)). L-NAME significantly reduced the hypotensive effect only of losartan. Vascular and cardiac hypertrophy were significantly attenuated with losartan or perindopril, but were unchanged with other treatments. The new analysis proposed here identifies differential effects on trends and cyclic variation and associations with regression of end-organ damage for losartan and perindopril compared with hydralazine plus hydrochlorothiazide. The method offers a powerful tool for detailed investigation of radio-telemetry data.

Animals↗
PubMed1999

Structural and functional assessment of small arteries in patients with chronic heart failure.

The physiological response to a chronically failing heart is the implementation of compensatory mechanisms intended to support blood pressure. These mechanisms, which are not fully understood, increase peripheral vascular tone, thus increasing the strain on the weakened myocardium. This study investigated the structure and function of small arteries from heart failure patients and controls without heart failure in an attempt to identify abnormalities associated with heart failure which may be related to these mechanisms. Small arteries were dissected from gluteal biopsies and studied using wire myography. Arterial morphological parameters were measured and concentration-response curves constructed for a number of vasoconstrictor and vasodilator agonists. Plasma concentrations of neuroendocrine hormones were also measured. There were no morphological differences between small arteries from control subjects and those from patients with chronic heart failure. In heart failure patients, vasoconstrictor responses to endothelin-1 were significantly reduced, although plasma endothelin-1 levels were increased. Arteries from heart failure patients also showed evidence of an impaired neuronal uptake mechanism, since blockade by cocaine had no effect on noradrenaline-induced vasoconstriction in these vessels. These results suggest that small-artery structure is not altered in chronic heart failure and so cannot account for the heightened vascular resistance in this syndrome. However, abnormal neuronal uptake and impaired vasoconstriction in response to endothelin-1 may be associated with the complex compensatory phenomenon involved in heart failure.

Acetylcholine↗
PubMed1998

ACE (I/D) genotype as a predictor of the magnitude and duration of the response to an ACE inhibitor drug (enalaprilat) in humans.

BACKGROUND: We have investigated the possible effects of contrasting ACE (I/D) genotypes on the responses to the ACE inhibitor enalaprilat in normotensive men. METHODS AND RESULTS: Subjects with DD (n=12) and II (n=11) ACE genotypes received an intravenous infusion of enalaprilat or placebo. Pressor responses to stepwise, incremental doses of angiotensin I were measured at 1 and 10 hours after dosing. The dose required to raise mean blood pressure by 20 mm Hg (PD20) was calculated individually, and the ratio of PD20 during enalaprilat to that during placebo (dose ratio, DR) was used for assessment of the extent of ACE inhibition. The pressor response was significantly attenuated at 1 hour after enalaprilat in both groups, but significant attenuation was evident at 10 hours after dose only in the II subjects. The DRs at both 1 hour (median, 5.43 versus 2.82, P=0.0035) and 10 hours (2.06 versus 0.84, P=0.0008) after enalaprilat were significantly higher in II subjects than in DD subjects. CONCLUSIONS: The effect of enalaprilat was significantly greater and lasted longer in normotensive men homozygous for the II ACE genotype. By multivariate analysis, ACE (I/D) genotype and plasma angiotensin II levels were predictive of >50% of the variation in response to ACE inhibition.

Adult↗
PubMed1998

Biochemical detection of left-ventricular systolic dysfunction.

BACKGROUND: In previous studies on the use of natriuretic peptides to detect left-ventricular systolic dysfunction, a higher rate of cardiac disorders in the control groups than in the study groups could have led to bias. We investigated the effectiveness of plasma N-terminal atrial natriuretic peptide (NT-ANP) and brain natriuretic peptide (BNP) concentrations to show left-ventricular systolic dysfunction in a random sample of the general population. METHODS: We randomly selected 2000 participants aged 25-74 years from family physicians' lists in Glasgow, UK. We sent all participants questionnaires. 1653 respondents underwent echocardiography and electrocardiography. We took a left-ventricular ejection fraction of 30% or less to show left-ventricular systolic dysfunction. NT-ANP and BNP were measured in plasma by RIAs. FINDINGS: 1252 participants had analysable electrocardiograms and echocardiograms, completed questionnaires, and available blood samples. Median concentrations of NT-ANP and BNP were significantly higher in participants with left-ventricular systolic dysfunction (2.8 ng/mL [IQR 1.8-4.6] and 24.0 pg/mL [18.0-33.0]) than in those without (1.3 ng/mL [0.9-1.8] and 7.7 pg/mL [3.4-13.0]; each p < 0.001). Among participants with left-ventricular systolic dysfunction, both symptomatic and asymptomatic subgroups had raised NT-ANP and BNP concentrations. A BNP concentration of 17.9 pg/mL or more gave a sensitivity of 77% and specificity of 87% in all participants, and 92% and 72% in participants aged 55 years or older. INTERPRETATION: Measurement of BNP could be a cost-effective method of screening for left-ventricular systolic dysfunction in the general population, especially if its use were targeted to individuals at high risk.

Adult↗
PubMed1998

Endothelin-1 has haemodynamic effects at pathophysiological concentrations in patients with left ventricular dysfunction.

OBJECTIVES: Plasma levels of immunoreactive endothelin-1 (ET-1) are raised in chronic heart failure. Whether plasma ET-1 contributes to the haemodynamic derangement found in chronic heart failure is not known. We investigated the effects of exogenous ET-1 on the pulmonary and systemic vasculature in patients with left ventricular systolic dysfunction (LVD), with or without overt heart failure. METHODS: ET-1 was infused at 1, 5 and 15 pmol/min into a distal pulmonary artery of ten patients with LVD to achieve plasma concentrations of ET-1 similar to those found in patients with heart failure and pulmonary hypertension. Haemodynamics were measured using a pulmonary thermodilution catheter and an arterial line. Intravascular Doppler and local pulmonary angiography were used to assess local pulmonary blood flow in the first four patients. RESULTS: Systemic haemodynamic changes occurred with ET-1 infusion: mean arterial pressure (100 +/- 3 [standard error of the mean]) to 107 +/- 3 mmHg; p < 0.01) and systemic vascular resistance (1699 +/- 118 to 2033 +/- 135 dynes s/cm5; p < 0.001) rose, while the cardiac index fell from 2.43 +/- 0.17 to 2.20 +/- 0.16 l/min/m2 (p < 0.002). Mean pulmonary artery pressure (21 +/- 2 mmHg) and pulmonary vascular resistance (151 +/- 14 to 147 +/- 14 dynes s/cm5) did not change however. CONCLUSIONS: Exogenous ET-1, when infused to achieve plasma concentrations similar to those in severe heart failure and pulmonary hypertension, causes systemic but not pulmonary vasoconstriction.

Aged↗
PubMed1998

Vascular smooth muscle cell polyploidy and cardiomyocyte hypertrophy due to chronic NOS inhibition in vivo.

To assess the vascular and cardiac response to NO (nitric oxide) synthase (NOS) blockade in vivo, Wistar-Kyoto rats (WKY) were treated for 3 wk with NG-nitro-L-arginine methyl ester (L-NAME; 10 mg.kg-1.day-1). L-NAME treatment induced hypertension that was associated with increased plasma renin activity. Flow cytometry cell cycle DNA analysis showed that aortic vascular smooth muscle cells (VSMC) from L-NAME-treated WKY had a significantly higher polyploid population compared with WKY controls. Using organ bath experiments, we have shown that aortic rings from L-NAME-treated WKY have an increased contractile response to phenylephrine and impaired relaxation to carbachol compared with control rings. NOS blockade in vivo caused a significant increase in cardiac and left ventricular hypertrophy. Northern mRNA analysis of the myocardium showed that L-NAME treatment caused reexpression of the fetal skeletal alpha-actin isoform without alterations in collagen type I expression, a pattern indicating true hypertrophy of the cardiomyocytes. These studies provide further insight to confirm that NO deficiency in vivo results in the development of vascular and cardiac hypertrophy.

Actins↗
PubMed1997

Potent in vivo inhibitors of rat renin: analogues of human and rat angiotensinogen sequences containing different classes of pseudodipeptides at the scissile site.

Using solid-phase methodology we have synthesised peptides based on the 8-14 or 6-14 human and rat angiotensinogen sequences, containing the following different isosteric units at the P1-P1' cleavage site: Leu-psi[CH2NH]Leu; Leu-psi[CH(OH)CH2]Val; Leu-psi[CH(OH)CH2]Leu and Leu-psi[CH(NH2)CH2]Val. In vitro, peptide Piv-His-Pro-Phe-His-Leu-psi[CH(OH)CH2]Leu-Tyr-Tyr-Ser-NH2(XXI) is the most potent inhibitor of rat plasma renin reported having an IC50 of 0.21 nM; it is a much weaker inhibitor of human renin (IC50 45 nM). Peptide Boc-His-Pro-Phe-His-Leu-psi[CH(OH)CH2] Leu-Val-Ile-His-NH2 (XX) was a highly effective inhibitor of rat renin in vivo. When infused (1 mg/kg/h) into two-kidney, one-clip chronic renal hypertensive rats, it lowered blood pressure and suppressed both plasma renin and angiotensin II. When given as a bolus (1 mg/kg) there was a divergence between the rapid rebound of renin levels and blood pressure, which remained suppressed. These results indicate that potent in vivo inhibitors of rat renin could be useful not only in examining the role of circulating renin but also in elucidating the equally important involvement of extracirculatory renin pools.

Amino Acids↗
PubMed1997

Brain natriuretic peptide is stable in whole blood and can be measured using a simple rapid assay: implications for clinical practice.

OBJECTIVES: To compare the stability of brain natriuretic peptide (BNP) to that of N-terminal atrial natriuretic peptide (NT-ANP) in whole blood and plasma stored under different conditions. To compare a rapid, simple, direct (unextracted) BNP assay to a conventional assay using plasma extraction. DESIGN: Blinded, prospective, comparative study. SETTING: Tertiary referral cardiology department. SUBJECTS: Forty two subjects (24 men, 18 women) comprising 28 patients with left ventricular systolic dysfunction (LVSD) ranging from mild to severe and 14 healthy volunteers. MAIN OUTCOME MEASURES: Stability of NT-ANP and BNP when stored as whole blood or plasma at room temperature over three days. Reproducibility of measurements. RESULTS: BNP was stable in whole blood stored at room temperature for three days; mean change in concentration -7.4% (95% CI 0.6 to -14.8), (direct), -6.3% (5.0 to -16.4), (extracted); whereas a significant decline in BNP concentration was noted in plasma stored at room temperature; -23.2% (-13.7 to -31.6), (direct); -14.4% (-3.2 to -24.3), (extracted). By contrast a small nonsignificant rise in NT-ANP concentration was noted both in whole blood and plasma stored at room temperature for three days; whole blood +8.6% (+22.3 to -3.5), plasma +6.3%, (23.2 to -8.4). The reproducibility of the BNP measurements, and particularly the rapid, direct, measurement, was superior to that for NT-ANP. CONCLUSIONS: BNP is shown to be stable in whole blood for three days and can be measured using a rapid, simple assay. Routine assay of BNP is feasible in ordinary clinical practice and may be of value to general practitioners and hospital based physicians in the diagnosis and management of patients with LVSD. Samples can be sent to a central laboratory without special handling requirements.

Adult↗
PubMed1996

Plasma angiotensin II, predisposition to hypertension, and left ventricular size in healthy young adults.

BACKGROUND: We studied the correlates of left ventricular mass (LVM) in 84 healthy young adults aged 16 to 24 years from the general population. Subjects were selected according to predisposition to hypertension into four groups with either high or low personal blood pressures and either high or low parental blood pressures. METHODS AND RESULTS: LVM was measured by echocardiography, and measurements of blood pressure, heart rate, body dimensions, and plasma concentrations of components of the renin-angiotensin system were made under resting conditions. LVM was similar in individuals predisposed to hypertension (high personal and parental blood pressures) and those with contrasting predisposition (low personal and parental pressures). Regression analysis of the combined groups showed that LVM correlated closely with body size, particularly lean body mass (r=.69, P<.0001) and systolic (r=.35, P<.0001) but not diastolic blood pressure. Plasma angiotensin II (r=.39, P<.0001), renin (r=.302, P<.01), and angiotensin-converting enzyme (r=.22, P<.05) showed significant correlation with LVM. Multiple regression analysis revealed that plasma angiotensin II was the most important component of the renin-angiotensin system and that its effect was independent of systolic blood pressure and body size. CONCLUSIONS: These findings provide evidence in humans that angiotensin II exerts a direct on myocardial size. This association may have important implications for the complications and treatment of left ventricular hypertrophy.

Adolescent↗
PubMed1996

Treatment of recurrent vesicourethral anastomotic stricture after radical prostatectomy with endourethroplasty.

We report our experience with successful treatment of 2 cases of severe recurrent vesicourethral anastomotic stricture after radical prostatectomy with endourethroplasty. Both patients had multiple failures of conventional treatments but have been free of stricture recurrence after endourethroplasty with 11 and 25 months follow-up, respectively. Follow-up urethroscopy showed open anastomotic segments with epithelialization after endourethroplasty in both patients. The patient who was continent prior to endourethroplasty remained continent afterward.

Aged↗
PubMed1996

Human fetal kidney morphometry during gestation and the relationship between weight, kidney morphometry and plasma active renin concentration at birth.

1. This study was designed to examine the changes in kidney morphometry during gestation in fetuses that were either appropriate or small for gestational age and the relationship between umbilical vein plasma active renin and kidney morphometry. 2. Serial ultrasound measurements of various morphometric and renal indices were performed in a cohort of 87 singleton fetuses from 22 to 38 weeks gestation. Blood was collected from the umbilical vein at delivery and active renin was measured from the plasma based on angiotensinogen I generated during incubation with plasma and ox renin substrate. 3. Growth in the longitudinal plane of fetal kidneys was similar in the small- and appropriate-for-gestational age groups; however, growth in the anterio-posterior, transverse and circumference planes of the kidneys was significantly slower in the small-for-gestational-age group after 26 weeks gestation. Differences in growth rate in the two groups were most marked between 26 and 34 weeks and persisted until delivery when the anterior-posterior diameter was significantly larger (P < 0.00001) in the appropriate-for-gestational-age group (26.1 +/- 2.5 mm compared with 19.8 +/- 2.6 mm). The mean umbilical vein active plasma renin concentration at delivery was significantly higher (P < 0.05) in the small-for-gestation-age group (274.4 +/- 32.9 mu-units/ml plasma) than in the appropriate-for-gestational-age group (164.9 +/- 28.3 mu-units/ml plasma). In addition, there were statistically significant inverse correlations between renin concentration and birthweight (r = -0.55, P < 0.001) and between renin concentration and kidney anterior-posterior diameter (r = -0.67, P < 0.001). 4. Fetal renal growth was slower in small than in appropriate-for-gestational-age fetuses. The period of 26-34 weeks gestation was that during which maximum fetal renal growth occurred. Umbilical vein plasma renin levels were higher in small-for-gestational-age fetuses. The findings of slow fetal renal growth rate and associated high renin concentrations seen in small-for-gestational-age fetuses could be implicated in an irreversible reno-vascular pathology leading to adult hypertension. We suggest that 26 to 34 weeks could be the "critical period' during which the insult that leads to in-utero programming for the development of adult hypertension occurs.

Birth Weight↗
PubMed1996

Plasma concentrations of inactive renin in adult life are related to indicators of foetal growth.

OBJECTIVES: To determine whether plasma concentrations of inactive and active renin in adult life are related to foetal development. DESIGN: A follow-up study of a group of men and women whose weight and other measurements of body size had been recorded at birth. SETTING: Sheffield, England. SUBJECTS: In total 148 men and women born in the Jessop Hospital, Sheffield, during 1939-40 and now aged 50-53 years. MAIN OUTCOME MEASUREMENT: Plasma concentrations of inactive and active renin in adult life. RESULTS: Plasma concentrations of inactive and active renin in adult life tended to be higher in people who had been large at birth. The strongest relationship was between concentrations of inactive renin and abdominal circumference at birth; the median plasma concentration of inactive renin was 88.5 mu/ml in people whose abdominal circumference at birth had been 13 inches (33.02 cm) or more compared with 61 mu/ml in people whose abdomens had measured 11.5 inches (29.21 cm) or less. CONCLUSION: Impairment of foetal growth is associated with lower plasma concentrations of inactive renin in adult life. Alterations in the activity of the renin-angiotensin system may be a mechanism by which reduced foetal growth leads to raised adult blood pressure.

Abdomen↗
PubMed1995

Influence of end-stage renal disease and renal transplantation on serum prostate-specific antigen.

OBJECTIVE: To evaluate the effect of dialysis and kidney transplantation on serum prostate-specific antigen (PSA) levels, and to compare these results with those from normal age-matched controls. In addition, to evaluate the efficacy of PSA and digital rectal examination (DRE) for detection of prostate cancer in patients on dialysis and following kidney transplantation. PATIENTS AND METHODS: Between January 1990 and July 1993 all men in the transplant programme over the age of 40 years who were undergoing pre-transplant evaluation or post-transplant follow-up underwent a yearly DRE and PSA evaluation. Twelve patients were evaluated pre-transplant and 70 patients were evaluated post-transplant. A total of 136 PSA levels were obtained (1.7 per patient). Patients with suspicious findings underwent further evaluation with transrectal ultrasound and biopsies if indicated. Controls were patients without known prostate cancer who had been evaluated in a Prostate Cancer Awareness Clinic. RESULTS: The average PSA values in the study groups were unaffected by either dialysis or transplantation when compared with age-matched controls. In addition, 12 patients who had been on dialysis at the time of their initial evaluation and who subsequently underwent transplantation did not show any difference in their average PSA values pre- or post-transplant. Three patients (4%) were found to have prostate cancer and two underwent radical retropubic prostatectomy. They are free of disease 24 and 36 months post-operatively and neither has experienced any decline in renal function. Immunosuppression was not modified. CONCLUSION: Transplantation and dialytic therapy do not appear to affect clinical serum PSA levels. PSA and DRE appear to be equally valid for detection of prostate cancer in patients on dialysis and post-transplant when compared with the general population. Finally, radical prostatectomy appears to be a safe and feasible treatment option in this group of patients.

Adult↗
PubMed1995

Enhanced pressor response to angiotensin I in normotensive men with the deletion genotype (DD) for angiotensin-converting enzyme.

The insertion (I)/deletion (D) polymorphism of the human angiotensin-converting enzyme gene has emerged as a genetic risk factor for ischemic heart disease. However, the functional consequences of this polymorphism in humans are not known. Ten normotensive men with the DD genotype and 10 with the II genotype participated in a study in which pressor responses to stepwise infusions of incremental doses of angiotensin I (Ang I) and Ang II and Ang II production during Ang I infusion were measured. Pressor responses were expressed as PD20, which reflects the angiotensin dose required to raise mean blood pressure by 20 mm Hg. The PD20 for Ang I in subjects with the DD genotype was significantly lower than that in II genotype subjects (8.8 versus 14.8 ng/kg per minute, P = .0091), whereas the PD20 for Ang II between the two groups did not differ significantly. The ratio of PD20 for Ang I and Ang II in DD subjects was significantly lower than that in II subjects (0.85 versus 0.96, P = .0452), and the venous levels of Ang II during Ang I infusion in DD subjects were significantly higher than those in II subjects (P < .01). Our study has shown increased pressor responsiveness to Ang I, probably as a consequence of the generation of increased Ang II levels, in subjects homozygous for the DD allele of the angiotensin-converting enzyme gene. This result may be relevant to the reported adverse cardiovascular risk conferred by the D allele, as it provides a mechanistic rationale for the association between this polymorphism and cardiovascular disease.

Adult↗
PubMed1995

Relation between renin and prorenin in plasma from hypertensive patients and normal people: evidence for different renin:prorenin ratios.

Renin and prorenin concentrations in plasma correlate closely, but the proportion of active renin to prorenin shows some variation in different forms of hypertension. The proportion of active renin to prorenin is higher in normal renin essential hypertensives and in patients with renal hypertension than in normal subjects, and it is lower in low renin essential hypertension and primary hyperaldosteronism. Plasma deficient in plasma prekallikrein shows a lower proportion of active renin than might be expected. Active renin and plasma angiotensin II concentration show a strong correlation while prorenin correlates weakly with plasma angiotensin II concentration.

Angiotensin II↗
PubMed1995

Vascular smooth muscle polyploidy in genetic hypertension: the role of angiotensin II.

Flow cytometry DNA analysis has been used to measure the percentage of aortic vascular smooth muscle cells in G2 + M phase of the cell cycle in mature stroke-prone spontaneously hypertensive rats (SHRSP). The effects of three different pharmacological interventions on the cell cycle parameters have also been studied. Vascular smooth muscle cells isolated from SHRSP have significantly elevated G2 + M phase of the cell cycle compared with cells from the normotensive reference strain, Wistar-Kyoto (WKY). This observation reflects an increased tetraploid and octaploid cell populations in vivo. Treatment with a combination of hydralazine and hydrochlorothiazide had no effect on the percentage of cells in G2 + M phase of the cell cycle. Treatments with angiotensin converting enzyme inhibitor, perindopril or AT1 receptor antagonist, losartan, resulted in an equivalent blood pressure-lowering effect to that obtained with hydralazine/hydrochlorothiazide. In contrast to hydralazine/hydrochlorothiazide, these two treatments resulted in a highly significant regression of vascular smooth muscle polyploidy in the SHRSP. We hypothesise that angiotensin II plays an important role in cell cycle regulation in that, alone or in conjunction with one of the inhibitory proteins, it is able to stop the cell cycle progression after endoduplication but before the cytoplasmic division. Pharmacological interventions which remove an excess of angiotensin II may allow the cells to re-enter the cell cycle thus resulting in the regression of vascular smooth muscle polyploidy and improved arterial compliance.

Angiotensin II↗