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Biomedical subjects

A M Heagerty

Publications and source records attributed to A M Heagerty.

At least 19 recordsLinked to original sources
PubMed1999

Impaired flow-dependent dilatation in distal mesenteric arteries from the spontaneously hypertensive rat.

1. The aim of the study was to examine the hypothesis that flow-dependent dilatation is impaired in distal mesenteric arteries from adult spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto rat (WKY) controls and to assess the role of nitric oxide (NO). 2. Arterial segments were cannulated, pressurized to 80 mmHg and allowed to develop spontaneous myogenic tone. Flow was increased incrementally in vessels from both strains and responses were also assessed before and after incubation with the NO synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME). Responses to flow in control vessels were also assessed before and after intraluminal perfusion with antibody-complement to disrupt the endothelium. 3. At a flow rate of 5 microliter min-1, arteries from the WKY dilated significantly (22 +/- 5%, P < 0.01, n = 29) compared with the diameter at zero flow, whereas arteries from the SHR did not (4 +/- 4%, n.s., n = 16). Incubation with L-NAME had no inhibitory effect on the responses to flow in either rat strain. In control arteries, antibody-complement treatment abolished the dilatation in response to both flow and acetylcholine (ACh, 1 microM). 4. We conclude that flow-dependent dilatation is impaired in distal mesenteric arteries from adult SHR compared with WKY controls. Furthermore, flow-dependent dilatation is endothelium dependent, but L-NAME insensitive, thus excluding the NO pathway in this abnormality. Impaired flow-dependent dilatation may contribute to the increased peripheral resistance in hypertension.

Animals↗
PubMed1998

Lipid second messengers derived from glycerolipids and sphingolipids, and their role in smooth muscle function.

The processes that link activation of an external receptor to the internal mechanisms that elicit a physiological response have been the subject of extensive investigation. It has been established that rather than just being an inert barrier to protect the cell from environmental damage, there are populations of phospholipids located within the plasma membrane that act as a reservoir for signalling molecules and when a receptor binds its appropriate activating ligand a chain of events is initiated which leads to the breakdown of these lipids and the release of second messengers. Such processes are rapid enough for physiological responses to be effected. The purpose of this review is to examine the profile of lipid second messengers derived from glycerophospholipids and sphingolipids. In the former class are included phosphoinositide and phosphatidylcholine and the latter includes sphingomyelin. Hydrolysis of such parent compounds is mediated by phospholipases and the profile of metabolites appears to be agonist specific and modulated by a number of mechanisms including heterotrimeric G-protein subunits, small G-proteins, alterations in intracellular calcium concentration, protein kinase C and tyrosine kinases. The recent interest in sphingolipids, particularly in vascular smooth muscle cells, has been provoked by the observation that ceramide and sphingoid base formation is observed in response to vasoconstrictor hormones.

Animals↗
PubMed1998

Structure and in vitro function of human subcutaneous small arteries in mild heart failure.

The structure and function of subcutaneous small arteries from patients with mild heart failure (n = 27) 6-43 mo after myocardial infarction were compared with vessels from healthy control subjects (n = 10). Patients were randomized to treatment with placebo or the angiotensin-converting enzyme inhibitor ramipril starting 3-10 days after myocardial infarction. Dissected arterial vessels were mounted on a wire myograph for measurement of morphology and isometric tension. Morphology was not different in arteries from the three groups. Responses to norepinephrine, angiotensin II, and electrical field stimulation were similar in arteries from placebo-treated patients with mild heart failure and control subjects. Similarly, endothelium-dependent and -independent relaxation was normal in arteries from patients with mild heart failure. Ramipril therapy was associated with functional alterations: vasoconstrictor responses to norepinephrine and angiotensin II were significantly enhanced compared with placebo (P < 0.001). These data suggest that vascular structure and function are not different in vitro in subcutaneous arteries from placebo-treated patients with mild heart failure. Angiotensin-converting enzyme inhibitor therapy is associated with enhanced vasoconstriction to norepinephrine and angiotensin II, which may reflect upregulation of receptor-mediated events.

Aged↗
PubMed1998

Endothelial dysfunction in human intramyocardial small arteries in atherosclerosis and hypercholesterolemia.

Vascular responses of human intramyocardial small arteries were examined in vitro to assess the influence of atherosclerosis and risk factors for coronary artery disease on endothelium-dependent relaxation. Recipient hearts were obtained from patients with ischemic (n = 14) and nonischemic (n = 13) cardiomyopathy undergoing heart transplantation. Small intramyocardial coronary arteries (mean internal diameter 313 +/- 11 micrometers) were mounted on a wire myograph for measurement of morphology and isometric tension. Vasodilation was examined after preconstriction with U-46619, a thromboxane A2 analog. Endothelium-dependent relaxation to acetylcholine and bradykinin was impaired in patients with ischemic compared with nonischemic cardiomyopathy (P < 0.01 and P < 0.001, respectively). Endothelium-independent relaxation to sodium nitroprusside was preserved. Incubation with L-arginine (3 mmol/l) did not improve endothelium-dependent relaxation to acetylcholine or bradykinin. With the use of stepwise multivariate analysis, hypercholesterolemia, but no other risk factor for atherosclerosis, was independently associated with impaired endothelium-dependent relaxation to acetylcholine (r = -0.50, P = 0.05) but not to bradykinin. Endothelial dysfunction in intramyocardial small arteries may predispose patients with nonobstructive epicardial atherosclerosis and hypercholesterolemia to myocardial ischemia.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

Dietary supplementation with marine fish oil improves in vitro small artery endothelial function in hypercholesterolemic patients: a double-blind placebo-controlled study.

BACKGROUND: Marine fish oils improve vascular function, but the mechanism of benefit is unclear. We conducted a study to examine the effects of fish oils given to hypercholesterolemic patients on small artery function in vitro. METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled trial, subcutaneous gluteal fat biopsies were taken from 16 hypercholesterolemic patients (serum total cholesterol, 7.97+/-0.16 mmol/L [mean+/-SEM]) and 12 age- and sex-matched control subjects (mean cholesterol, 5.11+/-0.34 mmol/L). Small arteries were mounted on a wire myograph for isometric tension experiments. Patients and control subjects were randomized to receive fish oil (Maxepa 5 capsules BID) or placebo for 3 months. A second biopsy was taken and the studies were repeated. Relaxation to acetylcholine was significantly improved in the hypercholesterolemic group given Maxepa but not in the placebo group (mean maximum relaxation before and after, 48+/-6.2% and 68.83+/-2.19%, P=.0054). The dysfunction was not restored to control values (84.3+/-5.2%, P=.0002). There was also a smaller but significant impairment in endothelium-independent relaxation provoked by sodium nitroprusside (P<.01). A good correlation between the increase in eicosapentanoic acid (n=3) in red cell membrane and improvement in relaxation in the hypercholesterolemic group given fish oils was seen (r=.781, P<.02). CONCLUSIONS: Marine fish oil significantly improved endothelial function in peripheral small arteries in hypercholesterolemia patients. This may provide a mechanism for the beneficial effects of these fatty acids in coronary heart disease.

Adult↗
PubMed1997

Involvement of tyrosine phosphorylation in endothelin-1-induced calcium-sensitization in rat small mesenteric arteries.

1. We have studied the effect of endothelin-1 stimulation on protein tyrosine phosphorylation levels in intact small mesenteric arteries of the rat and investigated the effects of tyrosine kinase inhibition on the contractile response to this agonist. 2. Endothelin-1 stimulated a rapid (20 s), sustained (up to 20 min) and concentration-dependent (1-100 nM) increase in protein tyrosine phosphorylation levels which coincided temporally with the contractile response in intact and alpha-toxin permeabilized small artery preparations. Tyrosine phosphorylation was increased in four main clusters of proteins of apparent molecular mass 28-33, 56-61, 75-85 and 105-115 kDa. Endothelin-1-induced protein tyrosine phosphorylation was independent of extracellular calcium, antagonized by the tyrosine kinase inhibitor tyrphostin A23 but not by the inactive tyrphostin A1. 3. In intact small arteries tyrphostin A23 inhibited the force developed to endothelin-1 at all concentrations studied; at higher concentrations (10 and 100 nM) the profile of contraction was altered from a sustained to a transient response. Tyrphostin A1 inhibited the contractile response to endothelin-1 at all concentrations except 100 nM; the profile of the response was not altered. Neither tyrphostin affected the transient phasic contraction induced by endothelin-1 (100 nM) in the absence of extracellular calcium. 4. In rat alpha-toxin permeabilized mesenteric arteries endothelin-1 caused a concentration-dependent increase in force in the presence of 10 microM GTP and low (pCa 6.7) constant calcium, demonstrating increased sensitivity of the contractile apparatus to calcium. Tyrphostin A23 inhibited this response by approximately 50%, tyrphostin A1 did not affect endothelin-1-induced calcium sensitization of force. 5. We conclude that increased tyrosine phosphorylation is important in the contractile response induced by endothelin-1 in intact small mesenteric arteries. Furthermore our data implicate activation of this signalling pathway in the tonic phase of contraction possibly through modulation of the sensitivity of the contractile apparatus to calcium.

Animals↗
PubMed1997

Transfection of cardiac muscle: effects of overexpression of c-myc and c-fos proto-oncogene proteins in primary cultures of neonatal rat cardiac myocytes.

1. Studies of cells transfected with specific expression vectors allow functions of specific gene products to be investigated. We first established optimum conditions for transfection of neonatal cardiac myocytes in primary culture. Increased proto-oncogene expression has been implicated in the development of cardiac hypertrophy; we therefore wished to examine the effects of overexpression of the c-myc and c-fos proto-oncogenes induced by cell transfection on cell growth. 2. Neonatal rat ventricular myocytes were transfected by electroporation, voltage and capacitance settings were optimized and these conditions were then used to transfect expression vectors encoding MYC and FOS proteins into this cell type. Effects on cell number, DNA synthesis and protein content were determined. 3. Increased expression of c-myc and c-fos in cells transfected with proto-oncogene expression vectors was confirmed by Northern and Western blotting. Increases in cardiac myocyte cell number, DNA synthesis and total cellular protein were observed in cells transfected with either c-myc or c-fos expression vectors compared with cells transfected with non-coding vectors. 4. Overexpression of MYC and FOS proteins results in hyperplastic rather than hypertrophic growth of the neonatal rat heart, providing evidence for a role of these proteins in the control of myocardial growth.

Animals↗
PubMed1997

Blood pressure parameters as determinants of small artery structure in human essential hypertension.

1. Adaptive changes in small arteries may be more closely correlated with pulse pressure than with systolic, diastolic or mean blood pressures in human essential hypertension. 2. An analysis was performed on the structure of small arteries, age and blood pressure measurements obtained from 56 patients with untreated essential hypertension and 56 matched normotensive volunteers to examine the association between age, blood pressure and small artery structural parameters. 3. Essential hypertension was associated with an increase in media thickness and a decrease in lumen diameter, resulting in an increase in media/lumen ratio. 4. There was a significant correlation between age and media/lumen ratio in normotensive volunteers but not in patients with essential hypertension. 5. There was no correlation between any blood pressure and structural parameter in normotensive volunteers. 6. Both diastolic and mean blood pressures in essential hypertension correlated with media/lumen ratio (P < 0.01); systolic blood pressure correlated less well (P < 0.02). However, pulse pressure did not correlate with media/lumen ratio, suggesting that it is not a significant determinant of small artery structure in untreated essential hypertension.

Adult↗
PubMed1997

Calcium sensitivity and agonist-induced calcium sensitization in small arteries of young and adult spontaneously hypertensive rats.

The sensitivity of the myofilaments to Ca2+ is increased during agonist-induced contraction of vascular smooth muscle. Given the important contribution of vascular tone to the elevation of peripheral resistance observed in genetic hypertension, we have investigated whether alterations in myofilament Ca2+ sensitivity occur in small arteries from spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) controls during the developmental and established phases of hypertension. Segments of mesenteric, renal, and femoral artery with an average lumen diameter <300 microm from 5- or 20-week-old rats were mounted in a wire myograph. Morphological measurements were made and the vessels permeabilized with Staphylococcus aureus alpha-toxin. Dose-response curves to increasing concentrations of Ca2+ were obtained and the ability of 100 nmol/L endothelin-1 (ET-1) or 10 micromol/L norepinephrine (NE) in the presence of 10 micromol/L GTP to enhance tension in response to low Ca2+ (pCa6.7) was determined. Systolic, diastolic, and mean blood pressures were higher in SHR than in WKY at 5 and 20 weeks. The media thickness:lumen diameter ratio was increased in mesenteric and femoral arteries from SHR compared with WKY at 5 and 20 weeks. There was no difference in media thickness:lumen diameter ratio in renal arteries or between 5- and 20-week animals in any vascular bed. The pCa curves were not different in mesenteric, renal, or femoral arteries from hypertensive compared with normotensive rats or between age groups, except in femoral arteries at 20 weeks, which exhibited a greater sensitivity to Ca2+ in SHR. Tension developed in response to maximal Ca2+ (pCa5.0) was greater in permeabilized mesenteric arteries from SHR compared with WKY at 20 weeks of age only; media stress was again similar in both strains but increased in older animals compared with younger animals in mesenteric arteries from WKY. The submaximal contraction induced by pCa6.7 was greater in femoral and renal than mesenteric arteries. GTP (10 micromol/L) augmented the tension developed to pCa6.7 in mesenteric arteries at 5 and 20 weeks and in renal arteries at 20 weeks. Addition of 100 nmol/L ET-1 or 10 micromol/L NE in the continued presence of GTP markedly increased tension in mesenteric arteries at 5 and 20 weeks. In renal arteries, 10 micromol/L NE enhanced Ca2+ sensitivity in the presence of GTP in SHR at 5 and 20 weeks and WKY at 5 weeks. In femoral arteries, there was a tendency for ET-1 and NE to increase Ca2+ sensitivity, but this increase was significant in WKY at 20 weeks (ET-1) and SHR at 5 weeks (NE) only. We have demonstrated that the sensitivity of the myofilaments to Ca2+ and ET-1- or NE-induced Ca2+ sensitization is not different in permeabilized small mesenteric, renal, or femoral arteries from SHR compared with WKY controls. Only in SHR mesenteric arteries at 20 weeks of age was there evidence of increased active tension in response to maximal Ca2+, despite structural differences, consistent with increased muscle mass in femoral arteries from SHR. We conclude that it is unlikely that a ubiquitous abnormality of the sensitivity of the contractile apparatus to Ca2+ or agonist-induced Ca2+ sensitization in vascular smooth muscle underlies the elevated total peripheral resistance associated with hypertension.

Aging↗
PubMed1996

Small artery structural alterations of patients with microvascular angina (syndrome X).

1. There is increasing evidence that a substantial number of patients who suffer from angina have normal epicardial arteries (Syndrome X), and it has been suggested that these individuals have a generalized disorder of small vessels not confined to the intramyocardial vasculature. 2. Small arteries were therefore obtained from biopsies of skin and subcutaneous fat from nine normotensive patients with Syndrome X and nine matched control subjects. Vessels were dissected and mounted as ring preparations in a myograph for morphological and functional assessment. 3. Morphological measurements revealed a significant increase in media thickness/lumen diameter ratio in arteries from patients with Syndrome X. Contractile responses to U46619 were similar in arteries from patients and control subjects. Endothelium-dependent relaxation induced with acetylcholine and bradykinin was greater in arteries from patients although differences were not statistically significant. Endothelium-independent relaxation induced by forskolin and sodium nitroprusside was not different. 4. In conclusion, these data demonstrate that subcutaneous small arteries from patients with Syndrome X are characterized by increased media thickness/lumen diameter ratios, although contractile responses were normal. Additionally, endothelium-dependent relaxation was not impaired in arteries from these patients. Thus, no significant functional abnormalities were associated with the observed structural differences.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Myogenic tone in mesenteric arteries from spontaneously hypertensive rats.

To investigate myogenic tone during the developmental and established phases of hypertension, segments of distal (6th order) mesenteric arteries from spontaneously hypertensive rats (SHR) at 5 and 20 wk were isolated and pressurized in vitro and compared with vessels from age-matched Wistar-Kyoto (WKY) control animals. At 5 wk, tone was significantly enhanced in the SHR. At 20 wk tone was no longer significantly increased over a wide pressure range, although arteries from the SHR were able to maintain diameter at all pressures studied, whereas vessels from the WKY exhibited forced distension at 180 and 200 mmHg. From the relative slope of the pressure-diameter relationship (myogenic index), no increase in peak myogenic responsiveness was observed in arteries from the SHR at either time point. Passive lumen diameters were significantly decreased in arteries from SHR at both time points. From the total and passive midwall circumference-tension relationships, total tension was observed at a reduced midwall circumference in the SHR, but increased absolute levels of total tension were not observed. The normalized midwall circumference-tension relationships in the two strains revealed increased total tension due to active tension development at a reduced normalized circumference at 5 wk in the SHR. At 20 wk the normalized midwall circumference-tension relationships in the two strains were identical. These results demonstrate that myogenic tone in mesenteric arteries is enhanced during the development of hypertension but not when it is established, except at high intraluminal pressures.

Aging↗
PubMed1996

Influence of isradipine and spirapril on left ventricular hypertrophy and resistance arteries.

Left ventricular hypertrophy is a common clinical feature in hypertensive patients and may be associated with structural changes in vessel morphology. In an open prospective trial, we evaluated 14 patients with previously untreated hypertension (163 +/- 2/104 +/- 2 mm Hg) and an echocardiographically determined left ventricular mass index of 141.6 +/- 5.2 g/m2, indicating left ventricular hypertrophy. We obtained a gluteal skin biopsy sample before starting treatment to investigate subcutaneous small-artery (approximately 200 to 400 microns diameter) morphology and function. Patients then received antihypertensive treatment with a combination of spirapril (3 or 6 mg) and isradipine (2.5 or 5 mg). Echocardiographic recordings were made after 6 months and 1 year, and a final biopsy was taken after 1 year. After 1 year, blood pressure was significantly reduced to 142 +/- 3/ 90 +/- 1 mm Hg (P < .001), and left ventricular mass index decreased significantly to 105.3 +/- 5.8 g/m2 (P < .001). Baseline media-lumen ratio (7.64 +/- 0.48%) was not markedly reduced (7.21 +/- 0.55%), although a decrease occurred in 7 of 12 evaluable patients. Norepinephrine-induced vasoconstriction was markedly reduced after 1 year. In conclusion, a significant regression of left ventricular hypertrophy was obtained after 1 year of treatment with spirapril and isradipine, whereas a similar reduction in medial thickness relative to lumen diameter of subcutaneous small arteries could not be observed in all patients. Reversal of structural changes in resistance vessels may require a longer treatment period in patients with proven left ventricular hypertrophy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Increased wall-lumen ratio of mesenteric vessels from the spontaneously hypertensive rat is not associated with increased contractility under isobaric conditions.

We investigated the morphological (wall-lumen ratio) and contractile characteristics of distal mesenteric arteries from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) controls at a distending pressure of 63% of the mean aortic pressure of each rat using a pressure arteriograph. The wall-lumen ratios obtained were compared with those obtained at a pressure of 100 mm Hg. Experiments were carried out at 5 and 20 weeks. Mean aortic pressure of SHR was significantly increased at 5 weeks compared with that of WKY and was further increased by 20 weeks. At 63% of mean aortic pressure, no difference in the wall-lumen ratio of the arteries was observed between strains at 5 weeks; at 20 weeks, the wall-lumen ratio of SHR arteries was significantly increased compared that in WKY arteries. The wall-lumen ratio of SHR vessels did not differ at 63% mean aortic pressure compared with 100 mm Hg at either 5 or 20 weeks, whereas this parameter was significantly reduced in WKY vessels at 100 mm Hg compared with 63% mean aortic pressure at 5 and 20 weeks. In the presence of spontaneous myogenic tone, there was a borderline reduction in the lumen diameter of SHR vessels compared with WKY vessels and with increasing norepinephrine concentrations at 5 weeks. At 20 weeks, lumen diameter between strains did not differ in the presence of myogenic tone nor with increasing norepinephrine concentrations. Similar results were obtained when vessels from both rat strains were pressurized to 80 mm Hg. Thus, the increased wall-lumen ratio in the distal mesenteric arteries from adult SHR compared with those from WKY is not associated with an increased contractility under isobaric conditions when studied at physiological distending pressure.

Animals↗
PubMed1996

Identification of protein kinase C isoforms in rat mesenteric small arteries and their possible role in agonist-induced contraction.

We have identified immunologically the protein kinase C (PKC) isoforms present in rat mesenteric small arteries, defined their distribution between particulate and soluble fractions, and studied their involvement in phorbol ester-induced contraction. Our analysis revealed the presence of the CA(2+)-dependent PKCs (alpha and gamma), Ca(2+)-independent PKCs (delta and epsilon), and the atypical isoform (zeta). PKCbeta could not be detected, whereas PKCgamma is likely to be of neural origin. All isoforms exhibited different distributions. PKCalpha, PKCepsilon, and PKCzeta were found in both particulate and soluble fractions. In contrast, PKCdelta was mainly in the particulate fraction, and PKCgamma was in the soluble fraction. Phorbol esters, which activate PKC and cause smooth muscle contraction, downregulated only the alpha and delta isoforms. This was associated with a parallel loss of contractile response to phorbol ester. The force developed to submaximal concentrations of noradrenaline was decreased after phorbol dibutyrate pretreatment, although the sensitivity and maximal response were unchanged. Phorbol ester pretreatment did not affect the contractile response to vasopressin. The sensitivity to non-receptor-mediated contraction, caused by k+ in the presence of prazosin, was slightly reduced by 4 alpha- and 4 beta-phorbol ester pretreatment. Maximal tension in response to this agonist was not affected. We conclude that PKCalpha and/or PKCdelta is necessary for phorbol ester-mediated contraction but is not essential for noradrenaline-, vasopressin-, or k(+)-induced contraction, demonstrating differences in the mechanisms involved in the contractile response between these agents.

Animals↗
PubMed1996

The effect of afterload and angiotensin II on proto-oncogene mRNA levels in the isolated working rat heart.

OBJECTIVES: The proto-oncogenes c-fos, c-myc and H-ras have been shown to rise in a characteristic pattern in the left ventricle undergoing hypertrophy in the coarctation model of experimental hypertension and there is some evidence to suggest that they might play a role in the initiation of hypertrophic growth. However, in vivo studies do not discriminate between the direct effects of pressure and pressure-independent trophic stimuli such as angiotensin II. To examine these influences separately we studied isolated working hearts exposed to different afterloads in the presence or absence of angiotensin II. METHODS: Hearts from normotensive female Wistar rats were perfused with a modified Krebs-Henseleit solution, with and without angiotensin II (100 nmol/1) and exposed to low (60 mmHg) or high (140 mmHg) afterload (n > 17/group). Proto-oncogene mRNA induction in the left ventricle was assessed by Northern blot analysis. RESULTS: Aortic pressures were 101 +/- 14/63 +/- 6 mmHg (mean +/- s.d.) with low and 175 +/- 13/93 +/- 20 mmHg with high afterload; hearts in both groups maintained a stable cardiac output over 240 min, except for high afterload hearts not perfused with angiotensin II, which showed a 59% drop by the end of the experiment (P < 0.001). There was a 50% (32%, 72%) (geometric mean and 95% confidence interval) increase of c-myc and 54% (27%, 86%) increase in c-fos, but a 32% (25%, 40%) suppression of H-ras with high (140 mmHg) as compared with low (60 mmHg) afterloads (P < 0.0001 for each). There was no significant difference in c-myc and c-fos induction with different levels of high afterload (110, 120, 140 mmHg), but for H-ras suppression progressively increased with increasing afterload (P = 0.003). At high afterload, levels of c-fos rose at 30 min and peaked at 60 min, c-myc continued to rise up to 240 min, and H-ras was suppressed at all four time points. The addition of angiotensin II (100 nmol/l) to the perfusate resulted in 18% (6%, 28%; P = 0.006) lower c-myc levels, 12% (-6%, 28%; P = 0.18) lower c-fos levels and an 11% (-0.1%, 24%; P = 0.056) increase of H-ras. CONCLUSION: The isolated perfused working rat heart is capable of performing stably for a period of at least 240 min at high afterload pressures comparable to those encountered in hypertension. A proto-oncogene induction similar to that seen in the hypertrophying heart can be induced by increased pressure alone, without the mediating effects of circulating angiotensin II. Hearts perfused with angiotensin II showed a more stable performance at high levels of afterload which was associated with a minor attenuation of pressure-induced changes in proto-oncogene expression.

Angiotensin II↗