Search PubMed⌕ Search

Biomedical subjects

P Friberg

Publications and source records attributed to P Friberg.

At least 91 records · Page 5Linked to original sources
PubMed1996

Mesenteric organ production, hepatic metabolism, and renal elimination of norepinephrine and its metabolites in humans.

This study used regional differences in plasma concentrations of norepinephrine and its metabolites to examine how production of the transmitter by sympathetic nerves, in particular, those innervating mesenteric organs, is integrated with metabolism by the liver and elimination by the kidneys. Higher concentrations of norepinephrine, its glycol metabolites 3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol and their sulfate conjugates in portal venous than arterial plasma indicate substantial production of norepinephrine by mesenteric organs (15.5 nmol/min). Much lower concentrations of norepinephrine and its glycol metabolites in plasma leaving than entering the liver indicate their efficient hepatic removal (20 nmol/min). Higher concentrations of vanillylmandelic acid in the hepatic outflow than inflow indicate that this metabolic end product is produced largely from the norepinephrine and glycol metabolites removed by the liver. Renal elimination of vanillylmandelic acid (18-20 nmol/min), produced mainly by the liver (17 nmol/min), and of 3-methoxy-4-hydroxyphenylglycol sulfate (7-9 nmol/min), produced largely by mesenteric organs (7 nmol/min), compromised 86-91% of the total renal elimination of norepinephrine metabolites. The results show that mesenteric organs produce about one-half of the norepinephrine formed in the body. The liver removes substantial amounts of circulating norepinephrine and its glycol metabolites and converts these compounds to vanillylmandelic acid, which is then eliminated from the body by the kidneys. The sulfate conjugates are also metabolic end products eliminated by the kidneys. However, these metabolites are produced by extrahepatic tissues, in particular, mesenteric organs, which represent a significant source of sulfate-conjugated norepinephrine and 3,4-dihydroxyphenylglycol, and the main source of sulfate-conjugated 3-methoxy-4-hydroxyphenylglycol.

Aged↗
PubMed1996

Therapeutic, but not low-dose, angiotensin-converting enzyme inhibition causes regression of cardiovascular changes in spontaneously hypertensive rats.

Therapy with angiotensin II-converting enzyme (ACE) inhibitors has been suggested to prevent cardiovascular hypertrophy in hypertension even in doses that are subantihypertensive. We investigated the effects of two different ACE inhibitors on blood pressure and cardiovascular changes during as well as after discontinuation of treatment in spontaneously hypertensive rats (SHR). SHR were treated with either enalapril (ENA) or ramipril (RAM) from age 12 to age 20 weeks. Each drug was given in either an antihypertensive (ENA 15 mg center dot kg-1, RAM 3 mg center dot kg-1) or a subantihypertensive (ENA 50 mu g center dot kg-1, RAM 10 mu g center dot kg-1) dose. Mean arterial pressure (MAP) was reduced with antihypertensive doses of ENA (26%) as well as RAM (21%). Regression of cardiovascular changes occurred as reduction in left ventricular (LV) weight/body weight ratio (25 and 21% for ENA and RAM, respectively), reduction in perfusion pressure at maximal vasodilation of the perfused hindquarter (PPdil, 17 and 17%), and reduction in maximal developed pressure (PPmax, 13 and 17%). These effects partly persisted 10 weeks after treatment was discontinued. However, treatment with subantihypertensive doses of ENA and RAM had no effect on MAP, LV/body weight ratio, PPdil, or PPmax. Overall, regression of cardiovascular parameters correlated closely to the decrease in MAP. Similarly, no changes in MAP, LV weight/body weight ratio, PPdil, or PPmax were noted when young SHR were treated with subantihypertensive doses of RAM from age 6 to age 12 weeks, during which time hypertension becomes established. At doses having equal effects on blood pressure, plasma concentrations of RAM were considerably lower than those of ENA. Skeletal muscle concentrations were very low or undetectable in comparison to plasma concentrations for both drugs. Therefore, both RAM and ENA caused regression of cardiovascular changes that could be explained by a concomitant reduction in blood pressure. This regression persisted for a considerable time after discontinuation of treatment. On the other hand, no specific antitrophic effects in the absence of blood pressure reduction was evident with either drug. Furthermore, despite substantial differences in plasma concentrations, RAM, and ENA administered chronically appeared to affect cardiovascular parameters equally in the adult SHR.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Cardiac insulin-like growth factor I and growth hormone receptor expression in renal hypertension.

The aim of the present study was to investigate the role of insulin-like growth factor I in the development of cardiac hypertrophy in two-kidney, one clip hypertension by relating growth hormone receptor and insulin-like growth factor I receptor mRNA levels to insulin-like growth factor I gene transcription using a solution hybridization/RNase protection assay. Two-kidney, one clip hypertension was induced in male Wistar rats, and experiments were performed 2, 4, 7, and 12 days after surgery. Systolic blood pressure was elevated 2, 7, and 12 days after clipping (P < .001). Left ventricular weights were increased 2, 4, 7, and 12 days after surgery (P < .01). Associated with the rise in blood pressure, left ventricular insulin-like growth factor I mRNA was increased 2, 7, and 12 days after surgery (P < .01). Furthermore, growth hormone receptor and insulin-like growth factor I receptor gene expression increased specifically in the left ventricle of renal hypertensive rats (P < .05 and P < .001, respectively). Left ventricular growth hormone receptor mRNA peaked 7 days after induction of renal artery stenosis. These results show that insulin-like growth factor I, growth hormone receptor, and insulin-like growth factor I receptor mRNA increase in the pressure-overloaded left ventricle of two-kidney, one clip rats, suggesting a role for insulin-like growth factor I and the growth hormone/insulin-like growth factor I axis in the development of cardiac hypertrophy.

Animals↗
PubMed1996

Normalization of total body and regional sympathetic hyperactivity in heart failure after heart transplantation.

BACKGROUND: Sympathetic nerve activity is increased in patients with severe heart failure. Whether this intense sympathoexcitation is normalized after heart transplantation, despite cyclosporine A treatment, is still unsettled. In the present study, regional sympathetic function in 12 patients with severe heart failure, awaiting heart transplantation, was compared with that in 15 heart transplant recipients and 12 healthy subjects. METHODS: Total and regional sympathetic activity in the heart and kidney were evaluated with isotope dilution, using steady-state infusion of [3H] norepinephrine. Sympathetic nerve traffic to skeletal muscle vascular bed was recorded intraneurally with microneurography. RESULTS: Total body, cardiac, and renal norepinephrine spillovers were high in the heart failure group (6792 +/- 455, 385 +/- 74, and 1554 +/- 114 pmol/min, respectively) as was muscle sympathetic nerve activity (82 +/- 5 bursts/min). Transplant recipients showed a marked reduction of total body (3200 +/- 307 pmol/min) and renal (747 +/- 169 pmol/min) norepinephrine spillovers and sympathetic nerve firing to skeletal muscle (22 +/- 6 bursts/min), none of which differed from healthy subjects. CONCLUSIONS: The augmentation of total body and regional sympathetic outflow to the kidney and skeletal muscle vascular beds, associated with a failing heart, was normalized after transplantation. Thus, sympathoexcitation in heart failure is reversible. Furthermore, because all heart transplant recipients received cyclosporine A, the findings do not support the concept that cyclosporine-induced hypertension is mediated by increased sympathetic nerve activity.

Adult↗
PubMed1996

Acute hypertension after nitric oxide synthase inhibition is mediated primarily by increased endothelin vasoconstriction.

OBJECTIVE: To determine the quantitative roles played by the different vasoconstrictor systems in the acute pressor response in conscious rats before and after inhibition of nitric oxide synthase with Nw-nitro-L-arginine methyl ester (L-NAME). METHODS: In conscious male Sprague-Dawley rats, previously instrumented with aortic and venous catheters, the contributions of the different systems were assessed by maximal cumulative pharmacological blockade of alpha 1-adrenoceptors (1 mg/kg prazosin intraperitoneally), AT1 receptors (30 mg/kg losartan intraperitoneally) and V1/V2 receptors (10 mg/kg [beta-mercapto-beta, beta-cyclopenta-methylenepropionyl1, O-Et-Tyr2-Val4-Arg8]-vasopressin per min intravenously). In addition, the contribution of endothelin-1-induced vasoconstriction in response to 100 mg/kg L-NAME intraperitoneally to the hypertension was assessed by administering 5-100 mg/kg ETA/ETB receptor antagonist PD 145 065 intravenously under three different conditions: as the last step of a series of antagonists in the cumulative pharmacological blockade after having induced the L-NAME pressor response; alone before L-NAME treatment; and alone after the full development of the L-NAME pressor response. A separate group of rats was treated acutely with 30 mg/kg losartan intraperitoneally or pretreated for 3 days with 30 mg/kg angiotensin I converting enzyme inhibitor enalapril via drinking water alone or in combination with 1% salt was used to assess the role of the renin-angiotensin system in the L-NAME-induced hypertension. RESULTS: Short-term administration of the combined ETA/ETB receptor antagonist PD 145065 did not change the arterial pressure under control conditions. Inhibition of the renin-angiotensin system, alpha 1-adrenoceptors or vasopressin receptors alone or in combination did not alter the magnitude of the L-NAME pressor response. In contrast, our results show that both treatments before and during acute nitric oxide synthase blockade hypertension using the ETA/ETB receptor antagonist PD 145065 abolished almost completely (approximately 85%) the pressor response. CONCLUSIONS: These studies indicate that the predominant mechanism of hypertension, at least in the acute phase, after acute nitric oxide synthase blockade with L-NAME is associated with a marked increase in ETA/ETB receptor activation rather than with increases in alpha 1, AT1 and V1/V2 receptor activation. It remains to be determined whether endothelin participates also in the chronic phase of nitric oxide-deficient hypertension.

Animals↗
PubMed1995

Plasma metanephrines in the diagnosis of pheochromocytoma.

OBJECTIVE: To examine whether tests for plasma metanephrines, the o-methylated metabolites of catecholamines, offer advantages for diagnosis of a pheochromocytoma over standard tests for plasma catecholamines or urinary metanephrines. DESIGN: Cross-sectional study. SETTING: 3 clinical specialist centers. PATIENTS: 52 patients with a pheochromocytoma; 67 normotensive persons and 51 patients with essential hypertension who provided reference values; and 23 patients with secondary hypertension and 50 patients with either heart failure or angina pectoris who served as comparison groups. MEASUREMENTS: Plasma concentrations of catecholamines (norepinephrine and epinephrine) and metanephrines (normetanephrine and metanephrine) were measured in all patients. The 24-hour urinary excretion of metanephrines was measured in 46 patients with pheochromocytoma. RESULTS: Pheochromocytomas were associated with increases in plasma concentrations of metanephrines that were greater and more consistent than those in plasma catecholamine concentrations. No patient with a pheochromocytoma had normal plasma concentrations of both normetanephrine and metanephrine. The sensitivity of these tests was 100% (52 of 52 patients [95% CI, 94% to 100%]), and the negative predictive value of normal plasma concentrations of metanephrines was 100% (162 of 162 patients). Tests for plasma catecholamines yielded eight false-negative results and a sensitivity of 85% (44 of 52 patients [CI, 72% to 93%]). The negative predictive value of normal plasma concentrations of catecholamines was 95% (156 of 164 patients). Tests for urinary metanephrines yielded five false-negative results and a sensitivity of 89% (41 of 46 patients [CI, 76% to 96%]). Because no statistical difference was noted in the number of false-positive results between tests for plasma metanephrines (15%) and tests for plasma catecholamines (18%), the specificities of the two tests did not differ. CONCLUSIONS: Normal plasma concentrations of metanephrines exclude the diagnosis of pheochromocytoma, whereas normal plasma concentrations of catecholamines and normal urinary excretion of metanephrines do not. Tests for plasma metanephrines are more sensitive than tests for plasma catecholamines or urinary metanephrines for the diagnosis of pheochromocytoma.

Adolescent↗
PubMed1995

Plasma metadrenalines: do they provide useful information about sympatho-adrenal function and catecholamine metabolism?

1. The clinical utility of plasma metadrenalines for examination of sympatho-adrenal function and catecholamine metabolism was assessed from plasma measurements of these metabolites in a number of clinical conditions (hypertension, cardiac failure, bilateral adrenalectomy and X-chromosomal deletions of the gene for monoamine oxidase), and before and during activation of sympathetic outflow or infusions of noradrenaline and adrenaline. 2. Plasma concentrations of normetadrenaline were less than 25% of those of noradrenaline, concentrations of metadrenaline and adrenaline were similar and those of sulphate-conjugated metadrenalines were 20- to 30-fold higher than free metadrenalines. Hypertensive patients had elevated plasma concentrations of adrenaline, noradrenaline and conjugated but not free metadrenalines. Cardiac failure patients had 2- to 4-fold increases in plasma noradrenaline and free and conjugated normetadrenaline. Adrenalectomy resulted in undetectable plasma concentrations of adrenaline, 91-97% decreases in free and conjugated metadrenaline and a 40% decrease in normetadrenaline relative to noradrenaline. Patients with X-chromosomal deletions of the gene for monoamine oxidase had 6- and 16-fold increases in plasma free and conjugated normetadrenaline and 2- and 4-fold increases in free and conjugated metadrenaline. 3. Infusion of catecholamines increased plasma concentrations of free metadrenalines by less than 6% of increases in precursor amines, indicating that most plasma normetadrenaline (84%) and metadrenaline (90%) is derived from metabolism of catecholamines before their entry into the circulation. Considerable O-methylation of catecholamines within the adrenals explains why sympatho-adrenal activation resulted in smaller proportional increases in plasma metadrenalines than catecholamines. 4. Plasma metadrenalines provide supplementary information about sympatho-adrenal activity to that provided by catecholamines, but are more useful for examination of the extraneuronal inactivation of catecholamines, particularly detection of neurochemical phenotypes in genetic disorders of catecholamine metabolism. Significant formation of metadrenalines within chromaffin tissue explains why measurements of plasma metadrenalines provide an extraordinarily sensitive method for diagnosis of phaeochromocytoma.

Adrenal Glands↗
PubMed1995

Splanchnic and renal sympathetic activity in relation to hemodynamics during isoflurane administration in pigs.

The aim of the present study was to investigate the impact of isoflurane on regional neurogenic mechanisms in the control of vascular tone. Therefore, regional determinations of sympathetic activity and hemodynamics were made in chloralose-anesthetized swine before and during administration of 1.4% isoflurane. Sympathetic activity was examined from spillover of norepinephrine (NE) into the circulation using an isotope dilution technique. Administration of isoflurane caused a marked decrease in mesenteric (65 +/- 9 pmol.min-1.100 g-1; P < 0.05) NE spillover. Renal NE spillover was moderately decreased (25 +/- 6 pmol.min-1.100 g-1; P < 0.05), whereas liver NE spillover did not change significantly during isoflurane administration, suggesting that liver sympathetic activity is maintained at this level of isoflurane anesthesia. Total body NE spillover decreased (13 +/- 2 pmol.min-1.100 g-1, P < 0.05). Thus, isoflurane affected sympathetic outflow in a regionally differentiated pattern. Significant correlations were found between total body, mesenteric, and renal NE spillovers and vascular resistances, supporting the concept that the observed reductions in vascular resistances in these circulations during isoflurane administration were in part a consequence of reduced sympathetic outflow. In the liver circulation, no correlation was found between NE spillover and liver portal or liver arterial vascular resistances. Liver arterial resistance was significantly reduced during isoflurane administration while liver portal resistance was unchanged. Administration of isoflurane caused reductions in cardiac output, renal, portal, hepatic arterial, and total hepatic blood flows, whereas mesenteric blood flow was unchanged. To summarize, isoflurane decreased mesenteric and renal NE spillover with concomitant reductions in vascular resistances.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Differential actions of desipramine on sympathoadrenal release of noradrenaline and adrenaline.

Spillovers noradrenaline (NA) and adrenaline (A) into plasma were examined before and after i.v. administration of 0.3-0.5 mg kg-1 desipramine (DMI) in 19 normal volunteers. DMI decreased the total body spillover of NA by 20 +/- 4%, but increased that of A by 45 +/- 10%. The results indicate differential sympathoadrenal actions of DMI, characterized by inhibition of NA release from sympathetic nerves and stimulation of A secretion from the adrenals. These effects of DMI provide an explanation for some of the cardiovascular complications of tricyclic antidepressant therapy and may also help to explain how sympathoadrenal function is differentially regulated.

Adult↗
PubMed1995

Regional myosin heavy chain expression in volume and pressure overload induced cardiac hypertrophy.

Although the overall shift towards the V3 myosin heavy chain (MHC) has been shown to be associated with cardiac hypertrophy, quantitative evidence describing regional expression is sparse. The aim of this study was to compare and contrast the regional ventricular myosin isoform expression in two distinct haemodynamic states: pressure and volume overload. Volume overload was achieved using an aortocaval fistula (ACF) model and pressure overload by two-kidney-one-clip (2K1C) hypertension. A separate group (UC-2K1C) had the clip removed 1 week prior to investigation. Sham operated rats (SHAM) served as controls. All groups were studied 4 weeks after surgery. Ventricular tissue samples (approximately 50 mg) were taken from the walls of the right ventricle (RV), septum and left ventricular (LV) free wall. Tissue samples (excluding RV) were divided into endocardium and epicardium, and myosin expression was determined using polyacrylamide gel electrophoresis. Cardiac hypertrophy was substantial in both LV (1.7-fold) and RV (1.9-fold) in ACF rats. The 2K1C rats had similar LV enlargement (1.6-fold) whereas RV hypertrophy was not as great (1.2-fold). Blood pressure (BP) was increased 65% in 2K1C rats, whereas there was no change in ACF rats with respect to SHAM animals. After unclipping (UC-2K1C), LV hypertrophy and BP had returned towards control levels. In general, V3 MHC expression was associated with increasing LV hypertrophy in both 2K1C and ACF models. However, there was a marked endo-epi differential (1.5:1) in the LV free wall and septum of 2K1C rats. In contrast, in ACF rats there was no differential V3 MHC expression in the LV or septal tissue, i.e. expression was similar in both endo- and epi-samples. Elevated expression of V3 MHC persisted despite normotension and regression of cardiac hypertrophy in UC-2K1C rats. Taken together with published results demonstrating that relative transmural myocyte hypertrophy in ACF rats (endo > epi) is in contrast to that seen in 2K1C rats (epi > endo), the present findings reveal that regional V3 myosin expression represents a distinct adaptational component of the overall cardiac hypertrophic response in both volume and pressure overload.

Animals↗
PubMed1995

Production and metabolism of dopamine and norepinephrine in mesenteric organs and liver of swine.

Concentrations of catecholamines and their metabolites in plasma entering and exiting mesenteric organs, liver, and kidneys were examined to assess the regional production and metabolism of catecholamines in anesthetized swine. Higher portal venous than arterial plasma concentrations of norepinephrine and its metabolites, 3,4-dihydroxyphenylglycol (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG), and of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), indicated substantial production of both catecholamines by mesenteric organs, representing 45-50% of total body production. Most dopamine was not metabolized to norepinephrine, suggesting a large nonnoradrenergic contribution to total body dopamine production. Concentrations of norepinephrine, DHPG, normetanephrine, and MHPG were lower in plasma exiting than entering the liver, whereas concentrations of the end-product of norepinephrine metabolism, vanillylmandelic acid (VMA), were higher in outflowing than inflowing plasma. Over 94% of the VMA removed by the kidneys was produced in the liver, consistent with the hepatic source of this metabolite. Removal of DOPAC and HVA by the liver exceeded removal by the kidneys or production by mesenteric organs, indicating greater hepatic than renal elimination of these metabolites from the body and underestimation of mesenteric organ dopamine production based on summed spillovers of dopamine metabolites from the liver into the systemic circulation.

Animals↗
PubMed1995

Hepatomesenteric release and removal of norepinephrine in swine.

Release and removal of norepinephrine (NE) by hepatomesenteric organs in anesthetized swine were examined using measurements of NE in arterial, portal, and hepatic venous plasma. NE spillover from the liver and mesenteric organs increased during splanchnic nerve stimulation, validating these measurements as indexes of sympathetic outflow. Administration of the neuronal uptake-blocking drug desipramine reduced mesenteric NE extraction more than hepatic extraction, suggesting that neuronal uptake was more important for NE removal in mesenteric organs than in the liver. Circulating NE was removed by the liver more efficiently than by mesenteric organs, whereas mesenteric NE spillover (2.46 nmol/min) exceeded liver NE spillover (0.74 nmol/min). Hepatomesenteric NE spillover represented 53% of total body spillover; NE clearance was 42% of total body clearance. Because of efficient hepatic extraction of NE released by mesenteric organs, the sum of mesenteric and hepatic NE spillovers (3.20 pmol/min) exceeded net hepatomesenteric spillover estimated using arterial and hepatic venous measurements alone (1.96 pmol/min). Thus valid assessment of the substantial amounts of NE released by hepatomesenteric organs requires separate examination of mesenteric and hepatic spillovers.

Animals↗
PubMed1995

Regional release and removal of catecholamines and extraneuronal metabolism to metanephrines.

Norepinephrine (NE) and epinephrine (E) are metabolized extraneuronally by catechol-O-methyl-transferase to the metanephrines (MNs), normetanephrine (NMN) and metanephrine (MN). Subjects in this study received infusions of tritium-labeled NE and E. Concentrations of MNs and catecholamines were measured in plasma flowing into and out of the heart, forearm, lungs, kidneys, mesenteric organs (gastrointestinal tract, spleen, and pancreas), liver, and adrenals to examine the regional production of MNs from circulating and locally released catecholamines. NE spillover from mesenteric organs and kidneys accounted for 64% of the spillover from all tissues. There was detectable spillover of E from most extraadrenal tissues, but 91% was from the adrenals. The production of MNs from locally released and circulating catecholamines varied widely among tissues. The liver made the largest contribution to removal of circulating NE (57%) and E (32%) and the largest contribution to the production of NMN (54%) and MN (37%) from metabolism of circulating catecholamines. In all other tissues more NMN was produced from locally released than from circulating NE. Thus, the metabolism of circulating NE was responsible for only 19% of the total production of NMN. An even smaller portion (6%) of plasma MN was derived from metabolism of circulating E. Most plasma MN (91%) was produced within the adrenals, which also provided the largest single source (23%) of NMN. The regional variation in extraneuronal production of MNs indicates considerable heterogeneity in how circulating and locally released catecholamines are handled by different tissues. The substantial contribution of the adrenals to the production of MNs explains the extraordinary sensitivity of these metabolites for the diagnosis of pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1995

Is there a third peripheral catecholaminergic system? Endogenous dopamine as an autocrine/paracrine substance derived from plasma DOPA and inactivated by conjugation.

In mammals, the sympathetic neurotransmitter is norepinephrine (NE), and the main adrenomedullary hormone is epinephrine (EPI). The sources and physiological roles of the third endogenous catecholamine, dopamine (DA), outside the brain have been obscure. Several lines of evidence suggest that in the periphery, rather than DA serving only as the precursor for the active compounds, released from sympathetic nerves and the adrenal medulla, DA may also act as an autocrine/paracrine regulator of local organ function. Thus, in the kidneys, most of DA formation appears to be from proximal tubular uptake of plasma DOPA, and binding of locally formed DA to dopaminergic receptors decreases Na/K ATPase activity and thereby accentuates natriuresis. In the gastric mucosa, DA may modulate sodium absorption and acid secretion. Recent clinical and laboratory animal evidence has indicated that the lungs and mesenteric organs contribute substantially to total body production and metabolism of DA. Generation of DA in non-noradrenergic, non-adrenergic cells can explain why human urine contains higher concentrations of DA and its metabolites than of NE and its metabolites. The vast preponderance of plasma DA in humans is sulfoconjugated. Since patients with sympathoneural failure have normal plasma levels of DA sulfate, one may speculate that the sulfoconjugating mechanism is relatively independent of sympathetic nerves and acts to localize DA effects and inactivate DA entering the circulation. These considerations lead to the concept of a third peripheral catecholaminergic system, where DA derived from plasma DOPA acts as an autocrine/paracrine substance and is inactivated by conjugation.

Animals↗
PubMed1995

Cardiac hypertrophy and related growth processes: the role of insulin-like growth factor-I.

For the heart and resistance vessels in general, increases in pressure load represent a major local stimulus for structural adaptation by elevating the wall tension against which cardiac and vascular smooth muscle contract. Under such conditions the wall thickness of the left ventricle and of the resistance vessels will increase, keeping wall tension per unit muscle layer (wall stress) normal. Alternatively, chronic volume overload and enhanced cardiac filling will induce a structurally based widening of the ventricular lumen. This pattern is associated with a corresponding increase in myocardial mass, so that the wall thickness to internal radius ratio remains more or less constant. A number of extrinsic influences such as the sympathetic nervous system, hormonal factors and growth factors, may superimpose their effects to modulate the final "trophic influence" on the cardiovascular system. Hyperactivity of the renin-angiotensin system, the sympathetic nervous system and various growth factors, have all been suggested to initiate cardiovascular growth in a way that is load-independent. The mechanisms involved in the conversion of a mechanical hypertrophic stimulus into an actual increase in tissue mass are likely to involve many substances and enzyme systems, including transcription factors, enzymes such as ornithine decarboxylase and various growth factors. The presence of the insulin-like growth factor-I (IGF-I) in the heart and vessels suggests a paracrine/autocrine role for this potent growth factor in the regulation of cardiovascular growth. The relationships between ornithine decarboxylase, cardiovascular hypertrophy and IGF-I gene expression are also reviewed.

Adaptation, Physiological↗
PubMed1995

Evidence in vivo for induction of cardiovascular growth processes by vasoconstrictor systems.

Greater smooth muscle growth is an important feature of the changes in blood vessel morphology in hypertension. The increase in vessel wall thickness: lumen ratio resulting from vascular hypertrophy impacts directly on total peripheral vascular resistance thereby influencing the severity of hypertension. The roles played by mechanical forces, vasoactive substances, growth factors and endocrine hormones in mediating hypertrophic vascular growth responses in vivo are currently under investigation. Here we review our current research aimed at: (a) defining the roles in vivo, of the renin-angiotensin system (RAS) and sympathetic nervous system (SNS), in the development of cardiovascular hypertrophy; (b) defining the importance of endogenous vasodilator systems, in particular, the ability of nitric oxide to inhibit trophic responses induced by the RAS and SNS and (c) examining whether trophic stimulation via the two neurohumoral systems as well as the antitrophic activity of the vasodilator systems is in part dependent on changes in blood pressure. In these studies the obligatory enzyme ornithine decarboxylase has proved to be a useful marker of ongoing hypertrophic cardiovascular growth.

Animals↗
PubMed1994

Renin-angiotensin system in neonatal rats: induction of a renal abnormality in response to ACE inhibition or angiotensin II antagonism.

In experiments designed to analyze cardiovascular structure in response to antihypertensive therapy with an ACE inhibitor, we decided to start very early in life with the aim to prevent blood pressure increases and the development of vascular structural changes. In these treated groups of rats we unexpectedly observed that after they were weaned, their water consumption and urine volume, respectively, increased substantially. The present study was designed to determine if inhibition of the renin-angiotensin system produced similar effects in different strains of rats, and focused on characterizing the abnormal fluid balance occurring as a consequence to neonatal treatment with ACE inhibitors or angiotensin II blockers. Three-day-old Wistar Kyoto (WKY), Wistar (WR) and spontaneously hypertensive rats (SHR) were given either saline, enalapril, captopril, losartan and the AT2 blocker, PD123319, in the same amount of volume for 20 days. Treatment was stopped and rats were examined with regard to renal morphology at 4, 14 and 30 weeks of age. In addition, water consumption, urine volume, urine electrolytes and osmolality were analyzed at 14 weeks of age, that is, 10 weeks off treatment. Early treatment with the ACE inhibitors, enalapril and captopril, and the AT1 blocker, losartan, but not the AT2 blocker, PD 123319, in the SHR and in the normotensive strains WKY and WR produced persistent, irreversible histopathological renal abnormalities in adult life, long after the rats had been taken off treatment. These abnormalities consisted of mainly cortical tubulointerstitial inflammation, various degrees of papillary atrophy and pelvic dilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗