Biomedical subjects

B Corman

Publications and source records attributed to B Corman.

At least 37 records · Page 2Linked to original sources

PubMed1998

Potentiation of receptor-mediated cAMP production: role in the cross-talk between vasopressin V1a and V2 receptor transduction pathways.

Cross-talk between the phospholipase C and adenylyl cyclase signalling pathways was investigated in Chinese hamster ovary (CHO) cells transfected with the V1a and V2 vasopressin receptors. Cell lines expressing V1a, V2, or both V1a and V2 receptors, were established and characterized. Stimulation of V2 receptors by vasopressin induced a dose-dependent increase in cAMP accumulation, whereas stimulation of V1a receptor resulted in an increase in intracellular calcium without any change in basal cAMP. The simultaneous stimulation of V2 and V1a receptors by vasopressin elicited an intracellular cAMP accumulation which was twice that induced by stimulation of V2 receptor alone with deamino-[d-Arg8]vasopressin. This potentiation between V1a and V2 receptors was mimicked by activation of protein kinase C (PKC) with PMA, and was suppressed when PKC activity was inhibited by bisindolylmaleimide. The potentiation was observed in the presence or absence of 1 mM 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor, implying that an alteration in cAMP hydrolysis was not involved. Vasopressin, as well as PMA, had no effect on the forskolin-induced cAMP accumulation, suggesting that PKC did not directly stimulate the cyclase activity. On the other hand, vasopressin, like PMA, potentiated the cAMP accumulation induced by cholera toxin, an activator of Galphas protein. These results suggest that, in CHO cells, vasopressin V1a receptor potentiates the cAMP accumulation induced by the V2 receptor through a PKC-dependent increase in the coupling between Gs protein and adenylyl cyclase.

1-Methyl-3-isobutylxanthine↗

PubMed1998

Aminoguanidine prevents age-related arterial stiffening and cardiac hypertrophy.

Aging is associated with cardiac hypertrophy and arterial stiffening possibly associated with accumulation of advanced glycation end products (AGEs). We evaluated the effect of aminoguanidine, an inhibitor of AGE production, on end-stage alterations of renal and cardiovascular systems. Normotensive WAG/Rij rats were treated from 24 to 30 mo with aminoguanidine and compared with a control group. Aminoguanidine did not modify body and kidney weights but prevented the age-related cardiac hypertrophy (heart weight: 1276 +/- 28 mg and 1896 +/- 87 mg in 24- and 30-mo-old control animals and 1267 +/- 60 mg in 30-mo-old treated rats, P < 0.01). The increase in mesangial surface in aging rats was reduced by 30% by aminoguanidine. Collagen content of the arterial wall increased between 24 and 30 mo whereas elastin content, media thickness, and smooth muscle cell number remained unchanged. Aminoguanidine did not affect these parameters; however, the age-related increase in aortic impedance (12.4 +/- 1.4 and 18.2 +/- 1.9 10(3).dyne.sec.cm-5 in control 24- and 30-mo-old rats, P < 0.01) and the decrease in carotid distensibility (0.79 +/- 0.11 and 0.34 +/- 0. 07 mm Hg-1 in control 24- and 30-mo-old rats, P < 0.01) were prevented by aminoguanidine. The prevention of arterial stiffening and cardiac hypertrophy in the absence of changes in collagen and elastin content suggests that the effect of aminoguanidine is related to a decrease in the AGE-induced cross-linking of the extracellular matrix.

Aging↗

PubMed1998

Angiotensin II potentiates vasopressin-dependent cAMP accumulation in CHO transfected cells. Mechanisms of cross-talk between AT1A and V2 receptors.

The V2 vasopressin and the AT1A angiotensin II receptors are respectively coupled to the adenylyl cyclase and the phosphoinositide pathways. The cross-talk between these two receptors and their transduction pathways were investigated in CHO cells transfected with cDNA of both AT1A and V2 receptors. In these cells, angiotensin II induced an increase in intracellular calcium, and vasopressin a rise in intracellular cAMP accumulation. The simultaneous addition of angiotensin II and vasopressin potentiated the production of cAMP by the V2 receptor. This potentiation was dose-dependent and, at a concentration of 10(-7) M angiotensin II, the accumulation of cAMP was 4-fold greater than that induced by 10(-7) M vasopressin alone. Such cross-talk occurred in the presence and absence of cyclic nucleotide phosphodiesterase inhibitors, indicating that inhibition of phosphodiesterase activity was not the principal cause of potentiation. This was confirmed by the absence of calcium-inhibitable isoforms of phosphodiesterases in CHO cells. The addition of angiotensin II to forskolin, which stimulates the adenylyl cyclase, did not modify the production of cAMP. Phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), partially mimicked, and staurosporine, an inhibitor of PKC, partially inhibited the effect of angiotensin II on vasopressin. Chelation of intracellular calcium with BAPTA-AM markedly reduced the potentiation of V2 receptor by angiotensin II. However, increase in intracellular calcium with thapsigargin did not modify the cAMP accumulation induced by vasopressin. It was concluded that, in CHO cells, activation of the AT1A receptor by angiotensin II potentiates the V2 receptor through activation of protein kinase C in the presence of intracellular calcium at a step located between the receptor and the adenylyl cyclase.

Angiotensin II↗

PubMed1998

The aging kidney: insights from experimental studies.

The rat provides a useful experimental model to study of the mechanisms of kidney aging. As in man, a wide diversity in the renal response to aging occurs in the rat, and because of this variability it is important to always specify experimental conditions, i.e., strain, gender, diet, and environment. Most aging rats display chronic progressive nephrosis, although the rate at which injury develops is highly variable. There are a number of known risk factors that potentiate injury, including male gender, genetic background, obesity, high protein/high calorie diet, and environmental exposure to pathogens. The causes of age-dependent glomerulopathy are multifactorial and include an imbalance between synthesis and degradation of extracellular matrix products, as well as hemodynamic alterations. Of importance, this damage is not inevitable and can be dissociated from normal kidney aging when optimal conditions for successful aging are provided. There is complex and sometimes contradictory information on vasoactive factors. It is, likely, however, that the activity of intrarenal AngII is somehow upregulated in the aging kidney of some, but not all, strains, and alpha 1-dependent renal nerve activity may also be enhanced. The endothelial vasodialtory prostaglandins and NO exert an increasingly important role in the maintenance of renal perfusion with advancing age, although their production may be diminished. In the future, we anticipate that comparison of rats with different genetic backgrounds will help to dissociate true aging from disease.

Aging↗

PubMed1997

Role of protein kinase C and carboxyl-terminal region in acute desensitization of vasopressin V1a receptor.

The role of protein kinase C activation and carboxyl-terminal region in rapid desensitization of the vasopressin V1a receptor was investigated in Xenopus oocytes. Preincubation of the oocytes with vasopressin or with the diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol (OAG), or direct injection of active protein kinase C, all blunted the calcium response of the V1a receptor. Truncation of the 51 terminal amino acids (S374STOP) modified neither the intracellular calcium response to vasopressin nor its desensitization by vasopressin or OAG. These data suggest that desensitization of the V1a receptor is mediated by PKC activation and that its carboxyl-terminal domain is not required for signal transduction and rapid desensitization.

Animals↗

PubMed1997

Circulating and cellular markers of endothelial dysfunction with aging in rats.

The influence of age on endothelial functional markers was investigated in rats. Angiotensin I converting enzyme (ACE) activity and nitric oxide synthase (NOS) mRNA expressions were examined in the lung and aorta of 10-, 20-, and 30-mo-old normotensive rats. These data were extended by the measurement of circulating endothelial cells. ACE activity was significantly decreased in plasma (P < 0.01) and lungs (P < 0.01) at 30 mo, whereas it was significantly increased in the aorta (P < 0.001) at this age. Conversely, ACE mRNA levels decreased with age in the lung (P < 0.05). The level of constitutive endothelial NOS (eNOS) mRNA was significantly reduced in the aorta of 30-mo-old rats (P < 0.05), but no changes were observed in the lungs. The level of inducible NOS (iNOS) mRNA in the aorta was significantly decreased in 20- and 30-mo-old rats (P < 0.01), whereas it was significantly increased in the lung at 30 mo (P < 0.01). Interestingly, eNOS was expressed approximately 30 times more (P < 0.001) in the aorta than iNOS, whereas in the lung it was only slightly higher than iNOS (35%; P < 0.001). Neuronal NOS mRNA expression was not modified with aging. In the aorta, guanosine 3',5'-cyclic monophosphate concentration followed NOS expressions and showed a significant decrease at 30 mo (P < 0.001). An increase in the number of circulating endothelial cells was observed in the oldest rats, possibly reflecting an increase in endothelial cell turnover with aging. The present results demonstrate that aging modifies the expression of endothelial markers implicated in the regulation of vasomotor tone. This age-dependent impairment of endothelial functions could contribute to the increased risk of pathological processes within the arterial wall associated with aging.

Aging↗

PubMed1997

Vasopressin V2 receptor mRNA expression and cAMP accumulation in aging rat kidney.

The ability of the kidney to regulate water balance is impaired with age, although the secretion of vasopressin is maintained in senescent animals. This suggests that the cellular response to antidiuretic hormone is reduced in aging kidney. To test this hypothesis, the relationship between the expression of the vasopressin. V2 receptor mRNA and adenosine 3',5'-cyclic monophosphate (cAMP) accumulation was investigated in the medullary thick ascending limb of Henle's loop (MTAL) of adult and aging rats. Tubular suspensions of MTAL were prepared from 10- and 30-mo-old female WAG/Rij rats. The accumulation of cAMP for maximal concentration of vasopressin was 34% larger in adult than in old animals (9.5 +/- 0.5 pmol/4 min, n = 16, and 7.1 +/- 0.6 pmol/4 min, n = 12, respectively). The concentration of vasopressin corresponding to half-maximal stimulation was similar in the two groups (0.66 +/- 0.20 and 0.52 +/- 0.09 nmol, n = 5, in adult and old animals), indicating comparable sensitivity of the renal cells with age. The age-related impaired response to vasopressin of the V2 receptor was specific for females and was not observed in males. Direct stimulation of adenylyl cyclase by forskolin induced a comparable accumulation of cAMP in adult and senescent rats. The V2 receptor mRNA level in the MTAL was constant between 10 and 30 mo whether the animals were normally hydrated or dehydrated for 2 days. These data indicate that, in MTAL, the age-related impaired cAMP accumulation by vasopressin would be linked to a change either in the translation of V2 mRNA or in posttranslational processing mechanisms or in the coupling between the V2 receptor and adenylyl cyclase.

1-Methyl-3-isobutylxanthine↗

PubMed1996

Glomerular capillary network of cortical nephrons is reduced in male but not in female aging rats.

The gender differences in the age-related changes of glomerular structures were determined in 10- and 30-month-old rats. In adult animals, glomerular volume, urinary space, capillary lumen area and mesangial domains of deep and superficial nephrons were larger in males than in females. Glomerular hypertrophy was evidenced with age in both males and females. This hypertrophy was greater in female (+70%) than in male (+20%) rats. Age-related hypertrophy concerned equally the urinary space and the glomerular tuft. The mesangial domain, however, increased more markedly than glomerular volume (+400%). As a result, the ratio of mesangial domain to glomerular section area was more than doubled between 10 and 30 months. In females, the age-related renal hypertrophy was associated with a constant total capillary lumen area in cortical nephrons. In contrast, the total capillary lumen area of male rats was reduced by 20% in superficial glomeruli and by 36% in deep glomeruli between 10 and 30 months. These morphological changes are in good agreement with the maintained glomerular filtration rate reported in old female rats and the decrease in renal blood flow and filtration rate reported in male rats. They suggest that the aging process does not similarly affect the vascular system of the kidney of male and female rats, although their mean blood pressure was comparable.

Aging↗

PubMed1995

Renin gene expression in the aging kidney: effect of sodium restriction.

The activity of the renin-angiotensin system as well as the ability of the kidney to retain sodium following salt restriction are reduced with age. The relationship between these age-related changes in renal function and the renin gene expression was presently investigated. The concentrations of renin and its mRNA were measured in kidney of 10- and 30-month-old control female WAG/Rij rats and of animals which were salt restricted for 4 days. In the senescent rats, the kidney renin concentration, like the plasma concentration of angiotensin II, was half that in adult rats. The intrarenal content of renin mRNA did not differ between 10- and 30-month-old animals, suggesting that the transcriptional rate of the renin gene is unchanged with age. During the early phase of adaptation to sodium depletion, the systemic angiotensin II concentration was not modified in either age groups. Four-days salt restriction did not significantly change the renal storage of renin. In contrast, this short term salt restriction induced a 2.3-fold increase in the renin mRNA in adult kidney, and a 1.9-fold increase in the senescent kidney. These data suggest that the age-related decrease in renal concentration of renin is linked to a modification in the rate of translation of renin mRNA, or to an alteration in the protein maturation. The difference in adaptation to the early phase of salt restriction with age should not be linked to changes in renin gene transcription, but more likely to a change in the tissue response to the local renin-angiotensin system.

Adaptation, Physiological↗

PubMed1995

Effect of aging on zinc and histidine transport across rat intestinal brush-border membranes.

The effects of aging on intestinal absorption of zinc and L-histidine were investigated in adult (10-month-old) and senescent (30-month-old) Wistar rats' brush-border membrane vesicles isolated from jejunum and ileum. Kinetic parameters of the zinc transport by the jejunal brush-border membrane were Jmax = 126 +/- 24 nmol.min-1.mg-1 protein and Km = 490 +/- 126 microM (10-month-old rats, n = 7). The transport of zinc was the same in the jejunum and the ileum of adult animals. In senescent rats, the zinc uptake was significantly lower in the distal part of the intestine than in the proximal one. A comparison of zinc uptake in 10- and 30-month-old rats showed that the transport capacity of the jejunum did not change with age but the ileal transport capacity decreased by 50%. This reduced uptake was associated with an increased cholesterol content of the brush-border membrane. The major site of L-histidine absorption was the jejunum, in both the 10- and 30-month-old animals. L-Histidine was co-transported with Na+. The kinetic parameters of the L-histidine carrier in the presence of Na+ were Jmax = 6.5 +/- 1.0 nmol.min-1.mg-1 protein and Km = 190 +/- 29 microM in the jejunum of 10-month-old rats (n = 12). Increasing the extra-vesicular concentration of zinc (0 --> 1 mM) reduced the uptake of L-histidine, and conversely increasing the concentration of L-histidine (0 --> 1 mM) reduced that of zinc: there was no evidence of transport of a complexed form [zinc-L-histidine] in brush-border membranes of the small intestine. During aging, the transport capacity of L-histidine by the jejunum decreased, whereas the ileal transport capacity was conserved. The modifications of absorptive capacity for zinc and L-histidine at the membrane level (loss of ileal function for zinc, and loss of jejunal function for amino acid) indicate that the normal aging of intestinal epithelial cells cannot be regarded as a decline in the overall transport of nutriments but as a combination of highly specific modifications of the various transport systems.

Aging↗

PubMed1995

Glycation of albumin with aging and diabetes in rats: changes in its renal handling.

Albumin glycation was investigated in old rats to elucidate the link between the preferential excretion of glycated albumin and age-related microalbuminuria. Postprandial blood glucose and the glycated albumin in the serum and urine of 3-, 10- and 30-month-old Wistar rats and in streptozotocin diabetic rats were determined. Blood glucose increased from 1.46 +/- 0.046 g l-1 in 3-month-old rats to 2.08 +/- 0.06 (10 months) and 1.75 +/- 0.23 (30 months) (P < 0.05). Albumin glycation level in the serum increased from 0.79 +/- 0.07 nmol HCHO/nmol albumin (3 months) to 1.41 +/- 0.14 (10 months) and 1.73 +/- 0.21 (30 months) (P < 0.05); urinary level increased from 1.63 +/- 0.39 nmol HCHO/nmol albumin (3 months) to 2.92 +/- 0.57 (10 months) and 2.39 +/- 0.36 (30 months) (P < 0.01). The percent glycated albumin in serum rose from 3.33 +/- 0.64 to 6.81 +/- 0.63 and 6.99 +/- 1.79% of total albumin (P < 0.05), whereas the urine percentage decreased from 12.81 +/- 3.97 to 12.64 +/- 2.87 and 2.63 +/- 0.97% (P < 0.05) in 3-, 10- and 30-month-old rats, respectively. Editing decreased with aging from 4.28 +/- 0.83 (3 months) to 1.84 +/- 0.32 (10 months) and 0.52 +/- 0.14 (30 months) (P < 0.01). Editing in microproteinuric diabetic rats was lower (0.95 +/- 0.08) than in 3-month-old control rats (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1995

Effects of chronic angiotensin I-converting enzyme inhibition on the relations between ventricular action potential changes and myocardial hypertrophy in aging rats.

We studied the effect of aging on cardiac hypertrophy and action potential duration (APD) in normotensive male WAG/Rij rats and evaluated the role of the renin-angiotensin system (RAS) in these effects. Cardiac hypertrophy occurs in 30-month-old rats, as indicated by an increase in heart weight, and APD gradually increases with aging in the epicardial region of the right and the left ventricle. Short-term treatment (1 month) with the angiotensin-converting enzyme inhibitor (ACEI) perindopril prevented age-related increase in heart weight/body weight ratio independent of its antihypertensive effects, but did not prevent changes in APD in 30-month-old rats. Our results show a dissociation of changes in cardiac mass from changes in APD during aging. The effect of ACEI on hypertrophy may be due in part to a direct angiotensin effect on cellular growth. Changes in APD are not related to hypertrophy but rather to the process of aging.

Action Potentials↗

PubMed1995

Increased production of tumor necrosis factor and interleukin-6 by arterial wall of aged rats.

Plasma cytokine levels are enhanced in aged animals and in elderly people. Vascular cells are known to be both targets and sources of cytokines. To investigate the effect of aging on vascular cytokine synthesis, we studied tumor necrosis factor (TNF), interleukin-6 (IL-6), and prostacyclin (PGI2) production by the arterial wall using organoid culture of aorta from 10- (n = 8) and 30-mo-old (n = 8) rats, after activation by lipopolysaccharide (LPS). Biological activity of TNF and IL-6 was measured in supernatant from incubated vessels. 6-Ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), a stable metabolite of PGI2, a secondary inflammatory mediator, was measured using enzyme immunoassay. In the absence of LPS, TNF production was undetectable in most animals and was not significantly increased in the aged group. By contrast IL-6 and 6-keto-PGF1 alpha productions, in the absence of LPS, were significantly greater in 30- (8,140 +/- 1,350 U/micrograms DNA and 23.2 +/- 6.4 ng/micrograms DNA, respectively) than in 10-mo animals (3,060 +/- 350 U/micrograms DNA and 8.4 +/- 1.6 ng/micrograms DNA, P < 0.01 and P < 0.05, respectively). LPS-induced production of TNF, IL-6, and 6-keto-PGF1 alpha was significantly increased in old rats, being increased respectively by 3.2-, 3.5-, and 2.4-fold at 1 ng/ml LPS, compared with the production in young rats. Because TNF and IL-6 are capable of regulating vascular cell function such as proliferation protein synthesis and contractility, these cytokines might play a major role in age-related remodeling of arteries and age-related vascular diseases.

6-Ketoprostaglandin F1 alpha↗

PubMed1995

Plasma proteins as biomarkers of the aging process.

This study was designed to characterize the rat serum proteins as biomarkers of the normal aging process. Crossed immunoelectrophoresis or electroimmunodiffusion quantitation of proteins was performed in rats aged 6, 12, 24, and 30 mo. Selection of healthy animals was based on confrontation of crossed immunoelectrophoresis patterns with those of experimentally inflamed young adults and with individual anatomopathological data. Convergence of inflammatory patterns and severe histological lesions was the exclusion criterion. Senescence-induced decrease was demonstrated for eight proteins [negative senescence reactants (SRs-)] and increase for six proteins [positive SRs (SRs+)]. Most SRs belonged to the class of proteins responsive to acute inflammation [acute phase reactants (APRs)]. One SR+, the thyroxine-binding globulin, a high-affinity thyroid hormone binder, emerged as a particularly reliable senescence biomarker, showing the highest aging-related variation (8-fold increase from 6 to 30 mo) and not belonging to the APR class. Chronic treatment with perindopril, an angiotensin I-converting enzyme inhibitor used in heart and renal disease therapy, significantly enhanced thyroxine-binding capacity, possibly by preventing age-related alterations of serum lipids. Serum protein patterns prove valuable both as indexes for selecting aging animals free from superimposed pathologies and as parameters of senescence-induced changes in protein biosynthesis.

Acute-Phase Proteins↗

PubMed1995

Effect of chronic ANG I-converting enzyme inhibition on aging processes. V. Intracellular calcium-vasoreactivity coupling.

Age-related changes in intracellular calcium ([Ca2+]i)-vasoreactivity coupling efficiency (i.e., perfusion pressure divided by [Ca2+]i) were studied in vitro in tail arteries of male, normotensive, WAG/Rij rats aged 6, 12, 24, or 30 mo; one-half of these were chronically treated with the angiotensin I-converting enzyme inhibitor (ACEI) perindopril (1 mg.kg-1.day-1 orally) from 6 mo onward. Arterial segments were perfused at a constant flow rate (perfusion pressure taken as an index of arterial tone) and loaded with the acetoxymethyl ester of fluorescent dye fura 2 (fura 2-AM). Increases in [Ca2+]i were measured simultaneously with vasoconstriction after stimulation with a depolarizing hyperkalemic solution or the agonists norepinephrine or serotonin. Age had no effect on increases in [Ca2+]i vasoconstrictor responses, or electromechanical coupling efficiency (hyperkalemic solution). Increases in [Ca2+]i after agonists were similar in all groups, but vasoconstrictor responses and pharmacomechanical coupling efficiency decreased with age. ACEI had no effect on vasoconstriction or [Ca2+]i signals. In conclusion, coupling efficiency after agonist stimulation decreased with age; ACEI had no effect on coupling efficiency.

Aging↗

PubMed1994

Sympathetic neurotransmission in the tail artery of aging rats.

1. Age-related changes in noradrenergic neurotransmission in the tail arteries of three rat strains: outbred Wistar (WI/Ico), inbred Wistar (WAG/Rij) and inbred Fischer (F344) have been compared in the present study. 2. The arterial noradrenaline content varied from 5 to 10 ng mg-1 wet weight amongst young (3 to 6-month old) representatives of each strain, but did not change with age. As protein content increased in senescent rats (24-month old) by 30-40%, arterial tissue growth would not appear to receive a concomitant increase in sympathetic growth leading to relative, age-related, structural sympathectomy in all strains. 3. The vasoconstrictor response to transmural electrical stimulation was diminished in adult and senescent rats of all strains. 4. As far as could be judged from the increase in noradrenaline release following perfusion with the alpha-adrenoceptor antagonist, phentolamine (1 microM), the presynaptic alpha 2-adrenoceptor-mediated inhibition of noradrenaline release was intact in old representatives of all strains. 5. With blockade of the two main systems which control noradrenaline release in the rat tail artery, viz, neuronal reuptake with cocaine (4 microM) and presynaptic alpha 2-adrenoceptors with phentolamine (1 microM), stimulation-evoked release of noradrenaline was similar at all ages and in all strains. This suggests that in the rat tail artery the basic mechanism of neuronal release of noradrenaline is not functionally modified by aging. 6 We conclude that as sympathetic nerve terminals are apparently intact in all three strains of senescent rats used, the age-associated deficit of alpha-adrenergic control of vascular function is postsynaptic in nature.

Aging↗

PubMed1994

Effect of chronic ANG I-converting enzyme inhibition on aging processes. I. Kidney structure and function.

The effect of angiotensin I-converting enzyme inhibition (ACEI) on the age-related changes in the kidney structure and function was investigated in rodents. Normotensive male Wistar (WAG)/Rij rats were treated with perindopril from the age of 6 mo to the day of killing at 12, 24, or 30 mo. Mean blood pressure, constant from 6 to 30 mo, was reduced by 19 mmHg in treated animals. With age, the major functional modifications were a decrease in glomerular filtration rate and in renal blood flow, a rise in intrarenal vascular resistance (IVR), a reduced tubular reabsorption of salts, and a progressive increase in proteinuria. ACEI significantly reduced IVR and proteinuria. From a structural point of view, the glomeruli showed 1) an increase in size, 2) a decrease in capillary surface, 3) a diffuse thickening of the glomerular basement membrane, 4) an expansion of the mesangial matrix, and 5) an accumulation of albumin droplets in podocytes inducing 6) a dispersed focal and segmental glomerulosclerosis which, at 30 mo, affected < 2% of glomeruli. Of these six age-related structural changes, ACEI delayed the appearance of the three latter changes.

Aging↗

PubMed1994

Effect of chronic ANG I-converting enzyme inhibition on aging processes. II. Large arteries.

The consequences of hypertension and aging on cardiovascular structure and function are reputed to be similar, suggesting that blood pressure plays a role in the aging process. However, the exact relationship between aging, blood pressure, and the arterial structure-function relationship has not been demonstrated. To test the effects of aging, renin-angiotensin system, and pressure on the arterial wall, 20 normotensive male WAG/Rij rats were killed at 6, 12, 24, and 30 mo of age and compared with similar groups treated with an angiotensin (ANG)-converting enzyme inhibitor (ACEI), perindopril. Arterial function was determined by a systemic hemodynamic study and by in situ measurement of carotid compliance. Arterial wall structure was determined by histomorphometric and biochemical methods. Aging did not significantly modify blood pressure, but ACE inhibition decreased blood pressure significantly from 6 to 30 mo. Plasma renin activity decreased with age and increased with ACEI. Plasma atrial natriuretic factor increased with age and was significantly decreased with ACEI. Absolute and relative left ventricular weight increased with age, and ACEI delayed these increases. Arterial wall stiffness increased with age, as shown by a significant decrease in systemic and local arterial compliance and by an increase in aortic characteristic impedance. The increase in carotid wall compliance after poisoning of smooth muscle contractile function (KCN) was greater in young (6- and 12-mo old) than in old (24- and 30-mo old) rats. Chronic ACEI treatment increased basal carotid compliance values slightly and did not change KCN carotid compliance. The aortic and carotid luminal size increased regularly with age. Aging was associated without any change in absolute elastin content. In contrast, collagen content increased with aging. Aging was also associated with an increase in medial thickness. Medial thickening was mainly due to smooth muscle hypertrophy. Aging was associated with intimal proliferation, which became progressively thicker and collagen rich. ACEI treatment did not prevent aortic lumen enlargement but significantly postponed the increase in medial and intimal thickening. Biochemical determinations of the aortic wall components confirmed the morphometric data. In conclusion, the age-dependent large artery enlargement and stiffening were observed both in normotensive rats and in those rats whose blood pressure was lowered by ACEI. This suggests that aging and blood pressure affect arterial wall structure and function by different mechanisms.

Aging↗