Cardiometabolic health after first pregnancy: Associations with social determinants of health. A nuMoM2b-HHS study.

Study objective: This study sought to evaluate the associations between social determinants of health (SDOH) at the time of first pregnancy and subsequent cardiometabolic health, defined as the development of metabolic syndrome. Design: nuMoM2b-HHS (Nulliparous Pregnancy Outcomes Study- Monitoring Mothers-to-Be-Heart Health Study) is an ongoing prospective cohort study. Setting: Eight academic medical centers enrolled and continue to follow participants. Participants: 4484 participants followed a mean of 3.2 years from the time of their first pregnancy. Interventions: N/a. Main outcome measure: Unadjusted and adjusted Poisson regression models with robust standard errors were used to obtain relative risks and 95% confidence intervals estimating the risk of metabolic syndrome for each baseline SDOH. In secondary analyses we examined the associations between SDOH and incident hypertension, obesity, and diabetes mellitus. Results: Metabolic syndrome developed in 13.6% of participants. Higher socioeconomic position at the time of pregnancy was associated with lower rates of metabolic syndrome [income > 200% poverty level aRR 0.55 (95% CI, 0.42-0.71), attainment of a bachelor's degree aRR 0.62 (0.46-0.84) or higher aRR 0.50 (0.35-0.71)], while being single [aRR 1.45 (95% CI, 1.18-1.77)] and having low health literacy were associated with a greater risk of metabolic syndrome [aRR 1.98 (95% CI, 1.28-3.07)]. Conclusions: Over a short interval following first pregnancy, participants accumulated high proportions of cardiovascular risk factors and metabolic syndrome, with some risk associated with SDOH. The impact of interventions addressing SDOH in pregnant people on cardiometabolic health should be tested as a means of reducing health inequities at the population level.

Intracellular angiotensin-(1-12) changes the electrical properties of intact cardiac muscle.

In the present work, the influence of intracellular injection of angiotensin-(1-12) [Ang-(1-12)] on the electrical properties of the intact left ventricle of Wistar Kyoto rats was investigated with electrophysiological methods. Particular attention was given to the role of chymostatin on the effect of the peptide. The results indicated that intracellular administration of the peptide elicited a depolarization of the surface cell membrane and an increase of duration of the action potential followed by the generation of early afterdepolarizations. The increment of action potential duration caused by Ang-(1-12) (100 nM) was due to a decrease of total potassium current recorded from single cardiomyocytes using the whole cell configuration of pCAMP. The decrease of potassium current was related to the activation of protein kinase C (PKC) because the specific inhibitor of kinase C, Bis-1 (10-9 M), abolished Ang-(1-12) effects on the potassium current. The question of whether the effect of Ang-(1-12) was related to the formation of Ang II by chymase was investigated.The results revealed that the intracellular administration of chymostatin, a chymase inhibitor (10-9 M) abolished the effect of intracellular Ang-(1-12) on the potassium current. Moreover, intracellular Ang II (100 nM), by itself, reduced the potassium current, an effect decreased by intracellular valsartan (100 nM). Valsartan (10-9 M) dialyzed into the cell abolished the effect of Ang-(1-12) (100 nM). These observations demonstrate that the effect of Ang-(1-12) on potassium current was related to the formation of Ang II and that the peptide has arrhythmogenic properties.

Isolated systolic hypertension in elderly WKY is reversed with L-arginine and ACE inhibition.

This study was designed to examine the preventability of progressive deterioration of cardiovascular structure and function in very old Wistar-Kyoto (WKY) rats with isolated systolic hypertension (ISH). To this end, male 18-month-old normotensive WKY rats were given either placebo or L-arginine (70 mg. kg(-1). d(-1)) and an ACE inhibitor (enalapril, 30 mg. kg(-1). d(-1)) for 6 months. These control and treated rats were studied at the age of 2 years by examining: cardiovascular mass and collagen content, cardiac function, and systemic and regional (including coronary) hemodynamics. Additional data obtained in adult, 35-week-old WKY are included for comparison. ISH associated with increased total peripheral resistance was found in the old, untreated WKY, and this was prevented by the combined treatment. The untreated rats also exhibited impaired left ventricular function, as denoted by increased left ventricular end-diastolic pressure and reduced maximal rates of rise and fall of left ventricular pressure. These functional changes were also ameliorated with the combined treatment. Coronary hemodynamics were also compromised in the untreated WKY; and therapy improved coronary flow reserve and minimal coronary vascular resistance in both ventricles of the old WKY in parallel with reduction of arterial pressure. Blood flow to various other organs was uncompromised in the old rats, although increased vascular resistances were observed in untreated old WKY with ISH. These changes were also improved by the combined therapy. Finally, therapy diminished left ventricular mass and collagen concentration in old WKY compared with the untreated WKY. However, when compared with the 35-week-old WKY, both groups of old WKY (untreated and treated) demonstrated myocardial fibrosis, depressed ventricular function, and compromised coronary hemodynamics. Therefore, L-arginine and ACE inhibitory therapy ameliorated the hypertensive and associated adverse cardiovascular changes in old WKY, although it failed to improve totally the progressive deterioration of cardiovascular structure and function that occurred with aging. The results suggest that different mechanisms may be responsible for the hypertension- and age-related cardiovascular changes, although they may appear to be similar.

Heart, aging, and hypertension.

Hypertension and aging adversely affect cardiovascular system and the heart is invariably involved. Manifestations of hypertensive heart disease and of the aging heart appear similar; ventricular hypertrophy, myocardial fibrosis, and impairments in ventricular function and coronary hemodynamics characterize both conditions. However, a great deal of evidence suggests that different underlying pathophysiological mechanisms may be involved. This report discusses most recent clinical and experimental findings and focuses on the alterations in nonmyocytic elements that are a part of heart involvement. Particular attention was given to factors that are responsible for exaggerated myocardial deposition of collagen that, by itself, may be responsible for ventricular dysfunction and impaired coronary hemodynamics in hypertensive and aging hearts. Newly developed therapeutical strategies, based on the most recent experimental and clinical studies, are also discussed.

Low-dose ACE with alpha- or beta-adrenergic receptor inhibitors have beneficial SHR cardiovascular effects.

BACKGROUND: There are no data regarding the prolonged effect of alpha-1 adrenergic receptor antagonists on ventricular collagen content and coronary hemodynamics in spontaneously hypertensive rats (SHR). This study, therefore, was designed to determine the effects of chronic treatment with the alpha-1 adrenergic receptor inhibitor doxazosin on SHR systemic and regional (especially coronary) hemodynamics, cardiovascular mass, and ventricular collagen. The effects of the combination of doxazosin with low-dose angiotensin-converting enzyme inhibitor were studied versus the alpha-1 antagonist alone. These effects were compared with those of a beta-1 adrenergic receptor inhibitor. METHODS AND RESULTS: Systemic and regional hemodynamics (radionuclide-labeled microspheres), left and right ventricular weight, hydroxyproline concentration, and aortic weight were measured at age 35 weeks. Doxazosin reduced arterial pressure and total peripheral resistance without changing left ventricular mass and collagen content, whereas monotherapies with the beta-1 antagonist metoprolol or a subdepressor dose of the ACE inhibitor enalapril were effective in reducing left ventricular mass and hydroxyproline without altering pressure. Doxazosin combined with the same low-dose ACE inhibitor reduced left ventricular mass and hydroxyproline without potentiating the hypotensive effect of doxazosin. By contrast, the combination of beta-1 antagonist with the low-dose ACE inhibitor reduced pressure, unlike either agent alone. Aortic weight index was significantly reduced only by doxazosin whether when used alone or with the ACE inhibitor. Low-dose ACE inhibitor with doxazosin or the beta-1 receptor antagonist as well as doxazosin alone decreased renal vascular resistance. CONCLUSION: These data show that the low subdepressor dose ACE inhibitor with an alpha- or beta-adrenergic receptor antagonist provides beneficial cardiovascular effects in SHR.

Coronary hemodynamic and ventricular responses to angiotensin type 1 receptor inhibition in SHR: interaction with angiotensin type 2 receptors.

This study was designed to determine the effects of angiotensin II type 1 (AT(1)) receptor inhibition on coronary hemodynamics and ventricular mass and hydroxyproline content and the additive effects of angiotensin II type 2 (AT(2)) receptor inhibition in spontaneously hypertensive rats (SHR). The selective AT(1) receptor antagonist candesartan (10 mg/kg per day) was administered alone or in combination with the AT(2) receptor antagonist PD 123319 (50 mg/kg per day) for 12 weeks. Control SHR received placebo for the same period. Left and right ventricular coronary blood flow, blood flow reserve, and minimal coronary vascular resistance were determined by using radiomicrospheres in male 35-week-old rats. Mean arterial pressure; total peripheral resistance; left and right ventricular, renal, and aortic weights; and hydroxyproline concentration were also determined. Candesartan reduced mean arterial pressure and left ventricular, renal, and aortic masses, as well as hydroxyproline concentration and minimal coronary vascular resistance of both ventricles. PD 123319 partially prevented the hypotensive effect of AT(1) receptor inhibition and reversed the effect on myocardial hydroxyproline concentration. These data suggest that AT(2) receptors contribute to the hypotensive and antifibrotic effects but not the coronary hemodynamic improvement or reduced left ventricular mass of AT(1) receptor inhibition in these adult SHR.

Abnormal renal vascular responses to dipyridamole-induced vasodilation in spontaneously hypertensive rats.

The objective of this study was to determine whether there were differences in hemodynamic responses of different vascular beds to systemic administration of dipyridamole between spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. To this end, systemic hemodynamics and organ blood flows (using labeled microspheres) were determined in conscious rats before and 10 minutes after dipyridamole (4 mg. kg(-1). min(-1)) infusion. In both the normotensive and hypertensive rats, the dipyridamole infusion reduced arterial pressure by approximately 20 mm Hg, associated with a decreased total peripheral resistance and an increased cardiac output. Renal blood flow decreased significantly in SHR after dipyridamole but remained unchanged or increased slightly in the WKY rats. There were no other differences in regional hemodynamics, including those of brain, liver, skin, and muscle, between the WKY and SHR. Antihypertensive treatment completely restored normal renal vascular response to dipyridamole. Previous reports had demonstrated an abnormal coronary hemodynamic response of the SHR. Our data demonstrate that, as with coronary hemodynamics, hypertension selectively induced alterations in renal vasculature. These findings may be of importance in identifying the earliest hemodynamic evidence of developing hypertensive nephrosclerosis.

Regional hemodynamics after chronic nitric oxide inhibition in spontaneously hypertensive rats.

BACKGROUND: Inhibition of nitric oxide (NO) synthase by L-arginine analogs is associated with elevation of blood pressure in rats. Because endothelium-dependent vasomotion in different vascular beds is not homogenous, the aim of this study was to characterize and compare regional hemodynamic responses in carotid, femoral, and renal vascular beds after chronic NO inhibition in spontaneously hypertensive rats. The possible role of circulating endothelin and renin angiotensin systems in mediating the effects of chronic NO inhibition was also studied. METHODS: Systemic and regional hemodynamics, left ventricular mass, plasma renin activity, and plasma endothelin-1 were determined in control and Nomega-nitro-Larginine methyl ester (L-NAME)-treated (10 mg/kg/day, 4 weeks) spontaneously hypertensive rats. RESULTS: L-NAME treatment increased arterial pressure and total peripheral and regional vascular resistance and decreased cardiac output, stroke volume, and regional blood flow. An increase in blood flow ratio and a decrease in vascular resistance ratio between carotid and renal as well as femoral and renal vascular beds in rats treated with L-NAME was found. Blood flow and vascular resistance ratios between femoral and carotid vascular beds remained unchanged. L-NAME increased plasma renin activity and left ventricular weight/body weight ratio, whereas plasma endothelin-1 was not modified. CONCLUSIONS: The results of this study showed that the renal circulation seemed to be more sensitive to the effects of chronic NO inhibition than carotid and femoral vascular beds. Simultaneous activation of the renin angiotensin system may further potentiate cardiovascular effects of chronic NO inhibition. No evidence that circulating endothelin-1 plays a role in this model of hypertension was found.

Pharmacologic agents on cardiovascular mass, coronary dynamics and collagen in aged spontaneously hypertensive rats.

OBJECTIVE: To determine whether antihypertensive treatment could alter hypertension and age-related progressive impairment of coronary hemodynamics and cardiac fibrosis in aged spontaneously hypertensive rats (SHR). DESIGN: Old SHR were given their respective therapy for 3 months. To differentiate between hypertension and age-related changes, a comparison was made between left and right ventricular indices since the right ventricle was not exposed to pressure overload. METHODS: Male, 65-week-old spontaneously SHR were divided into three groups and were given either vehicle, felodipine (30 mg/kg per day) or enalapril (30 mg/kg per day). After 12 weeks of the respective treatments, systemic and coronary hemodynamics (radionuclide-labelled microspheres), right and left ventricular and aortic mass indices, and right and left ventricular hydroxyproline concentrations (an estimate of collagen) were determined. RESULTS: Arterial pressure and total peripheral resistance were reduced to the same extent in SHRs treated with either felodipine or enalapril; however, compared to the control rats, enalapril was more effective in reducing left ventricular and aortic mass indices. Both agents also improved coronary hemodynamics of both ventricles in aged SHR but enalapril was more effective as indicated by a greater increase in coronary flow reserve and a greater decrease in minimal coronary vascular resistance. Furthermore, enalapril but not felodipine reduced left ventricular hydroxyproline concentration; and right ventricular hydroxyproline concentration increased with felodipine but remained unchanged with enalapril. CONCLUSIONS: Both enalapril and felodipine ameliorated adverse cardiovascular effects of hypertension in the aged SHRs within 12 weeks, as demonstrated by reduced arterial pressure, diminished left ventricular mass, and improved coronary hemodynamics. Enalapril also decreased aortic mass and left ventricular collagen concentration and appeared to be more effective in improving coronary hemodynamics than felodipine, possibly as a result, in part, of reduced myocardial fibrosis.

L-arginine reduces tubular cell injury in acute post-ischaemic renal failure.

BACKGROUND: The pathophysiology of renal ischaemia, resulting in tubular cell injury and leading to acute renal failure (ARF), remains unclear. An ever-increasing number of investigations focus on a possible role of nitric oxide (NO) in regulating circulation during ARF. In this context, we investigated the influence of chronic stimulation or inhibition of NO synthesis, or both, on haemodynamic parameters, histology and plasma renin activity (PRA) after ischaemia-reperfusion injury of rat kidneys. METHODS: Experiments were performed on adult, male Wistar rats. Before induction of ARF, a group of animals was treated with a NO synthesis inhibitor (L-NAME) and another group was treated with a precursor of NO synthesis (L-arginine). The animals received those substances for 4 weeks. Control groups received the same amount of tap water for 4 or 8 weeks and were divided into groups with ARF (4 weeks--ARF group and 8 weeks ARF group) and a sham-operated group. Another group of rats was treated first with L-NAME and then with L-arginine in their drinking water, for 4 weeks for each of these two substances. All parameters were evaluated 24 h after the induction of ischaemic ARF or the sham operation. RESULTS: Our results show that such long-term stimulation of NO release by L-arginine improved renal haemodynamics in the ischaemic form of ARF. Renal blood flow (RBF) increased by 96% in the L-arginine-treated rats with ARF compared with the group with ARF alone. Inhibition of NO synthesis worsens renal haemodynamics after ARF. However, this aggravation can be reversed by L-arginine. The rate of water reabsorption was reduced in all groups with ARF, but this reduction was least in the group treated with L-arginine. The rate of Na+ reabsorption was reduced in all groups 24 h after renal ischaemia, but a significant decrease was observed after the inhibition of NO synthesis. Histological examination of the kidney specimens showed that morphological changes were least in the rats treated with L-arginine, when compared with all other groups with ARF. Nevertheless, the lesions were most prominent in the L-NAME+ARF group. In this group, the areas of corticomedullar necrosis were more widespread in comparison with other groups, especially the L-arginine group where only swelling of the proximal tubular cells was observed. Treatment with L-NAME was not accompanied by any significant alteration in the plasma concentration of angiotensin I (ANG I), while in the group treated with L-arginine ANG I had a tendency to decrease. CONCLUSIONS: Acute post-ischaemic renal failure may be alleviated by administering the NO substrate (L-arginine). NO acts cytoprotectively on tubular epithelial cells in ischaemia--reperfusion injury of rat kidney. Evidence of this comes from both histopathological findings and increased tubular water and sodium reabsorption. However, inhibition of NO synthesis (provoked by L-NAME) worsens renal haemodynamics and aggravates morphological changes after ARF. These aggravations can, however, be reversed by L-arginine.

Effects of captopril on morphologic changes in kidney of spontaneously hypertensive rats with adriamycin nephropathy.

Antihypertensive therapy has been shown to slow down the progression of chronic renal failure. Angiotensin converting enzyme inhibitors and calcium antagonists have been emphasized as the agents with the most protective effect. Our previous study showed that captopril slowed down renal function deterioration in the early course of adriamycin (ADR) nephropathy in spontaneously hypertensive rats (SHR). The present study was undertaken with the aim to examine morphologic changes associated with that slower renal function deterioration. Adult (24 weeks) female SHR were randomly divided into the following groups: the control group (n = 12) was given tap water to drink; the adriamycin (ADR) group (n = 25) was treated with ADR; the ADR-captopril (ADR-C) group (n = 27) was treated with ADR and thereafter with captopril (60 mg/kg/day). Rats were sacrificed at weeks 6, 12 and 18 and histologic analysis was semiquantitatively performed. In the control group the glomeruli exhibited only minor changes at the end of the study. In the ADR group slight glomerular mesangial hypercellularity appeared in the sixth week and progressed in focal and segmental sclerosis. Some glomeruli showed segmental proliferation and increased fibrular matrix of a tuft adherent to a fibrocellular crescents. In the ADR-C group, glomeruli with a slight increase of mesangial matrix were seen at the end of the sixth week, mesangial hypercellularity developed until the end of the sixth week, mesangial hypercellularity developed until the end of the 12th week and segmental glomerulosclerosis until the end of the study. Semiquantitative analysis revealed that the mean semiquantitative scores for mesangial expansion and glomerular sclerosis were significantly lower in ADR-C group than in ADR group throughout the study. We concluded that captopril slowed down mesangial expansion and reduced the development of glomerular sclerosis.

Gastrin producing G-cells after chronic ethanol and low protein nutrition.

Male Wistar rats, (2 months old), randomly divided according to the diet offered to four groups (C-control; A- alcoholized, PD-protein-deprived, A-PD- alcoholized protein-deprived). In group A and A-PD rats, the number of gastrin producing G-cells was significantly lower. The volume density of G-cells was significantly decreased in alcoholic rats. Fasting serum gastrin level (FSGL) significantly raised due to combined effect of alcohol consumption and protein malnutrition. In group A rats, the profile area of G-cells and their nuclei increased. In PD rats, the profile area of G cells also increased. There were no differences in nucleus/cell ratio due to alcohol ingestion alone, but it decreased significantly in PD and A-PD rats. Pale and lucent types of granules were predominantly seen in G-cells of animals of group A and A-PD. Mean diameter of granules increased in A, PD and A-PD rats. Other endocrine cells (ECL, D, EC) also decreased in number in A rats. Somatostatin producing D-cells decreased significantly in A-PD rats, both in fundic and pyloric mucosa.

The effects of long-term low-protein intake on gastrin cells of the rat antral mucosa during adulthood.

The effect of experimental protein malnutrition on gastrin producing cells in the antral part of the stomach was studied in male Wistar rats. Isoenergetic diets containing 25% (C-25) or 6% (PD-6) were given in isocaloric amounts during a 4-month experiment. All rats were offered drinking water ad libitum. The results showed that the long-term protein diet did not produce changes in the gastrin cell number. At the ultrastructural level G cells exhibited a decreased size of the nucleus. They were found to have an increased total granule volume density but the volume density of dense-cored granules was lower. The serum gastrin levels were significantly lowered by feeding the low protein diet. These changes are compatible with decreased functional activity of G cells under long-term protein deprivation.

Factors affecting the ability of the renal medulla to exert an antihypertensive function.

To examine whether changes in renomedullary osmolality and the activity of the renin-angiotensin system may influence the ability of the renal medulla to exert an antihypertensive function, rats were exposed to several manoeuvers. These affected either the medullary osmolality or the renin-angiotensin system (salt or saccharose load, salt depletion, treatment with captopril alone or in combination with salt depletion). A comparison of the antihypertensive capacity of the renal medulla was studied by transplanting renal medullae from the various groups into one-kidney one-clip hypertensive rats. A significant and quantitatively similar reduction in blood pressure was observed in hypertensive rats that received transplants of the medullae from control, salt or saccharose loaded rats and captopril treated rats. In contrast, medullae from salt depleted rats did not affect blood pressure when transplanted into hypertensive animals. The addition of captopril restored the antihypertensive function of renal medulla in salt depleted rats. The results do not support the view that osmolality of the renal medulla regulates its antihypertensive capacity, and suggest that angiotensin II may restrain renomedullary antihypertensive function.

Rat pancreatic B-cells after chronic alcohol feeding. A morphometric and fine structural study.

Quantitative analysis of the light microscopic and fine structure of rat islet B-cells was carried out in chronic alcoholism. Absolute pancreatic weight and volume were similar in groups C (control) and E (ethanol), but relative pancreatic weight in group E rat was decreased. The results for fasting blood glucose and insulin levels were similar in the two groups of animals. There was a significantly reduced total pancreatic islet volume in E rats. The total number of endocrine cells both per islet and per microns2 of islet was similar in the two groups of animals. The volume density and number of B-cells per islet and per microns2 of islet were not changed in ethanol-treated rats as compared with the control. On the other hand, diameter, surface area and volume of the B-cells and their nuclei were found to be statistically significantly decreased. Histological examination revealed that islet blood vessels were dilated in alcoholic rats. Over the 4-month period of ethanol intake a significant decrease in cell profile area, nuclear profile area and volume density of cytoplasmic granules and an increase in the profile area and volume density of endoplasmic reticulum occurred. The gross histological alteration seen in most B-cells of the ethanol-treated rats was irregularity of the nuclear envelope with deep invagination and with margination of heterochromatin and many empty granules or granules without clear electron dense crystals of insulin. The present results indicate some optical and structural abnormalities of B-cells in chronic alcoholism that may be related to cell dysfunction and may contribute, at least in part, to the endocrine pancreas functional disturbance.

Effects of captopril and hydralazine on progression of adriamycin nephropathy in spontaneously hypertensive rats.

The effects of captopril and hydralazine on morphologic changes and clinical course of adriamycin nephropathy in spontaneously hypertensive rats (SHR) were examined. The rats were followed for 18 weeks after adriamycin injections. At week 1 they were randomly assigned to receive no antihypertensive treatment, captopril 60 mg/kg per day or hydralazine 6 mg/kg per day. A control group of SHR not treated with adriamycin was also included in the study. Both antihypertensive agents normalized systemic blood pressure, but failed to prevent proteinuria, mesangial expansion and renal failure progression. At the end of the study all adriamycin-treated groups had the same degree of renal failure irrespective of whether blood pressure was well controlled with captopril or hydralazine or whether hypertension persisted. Nevertheless, antihypertensive therapy slowed down renal function deterioration in the early stage of adriamycin nephropathy. Treatment with captopril also reduced the development of glomerular sclerosis.

Effect of chronic alcohol feeding on the ultrastructure of rat peripheral blood neutrophils: a morphometric study.

Morphometric methods were used to analyze the ultrastructural characteristics of peripheral blood polymorphonuclear neutrophils (PMN) in 10 rats chronically consuming ethanol and 20 rats fed an isoenergetic standard diet (10 ad libitum and 10 pair fed control rats). Morphometric measurements were made, after a 4-month experimental period, of the following: the profile area of the cell, nucleus and cytoplasm; nucleus to cell profile area; volume density of the nucleus, cytoplasm, mitochondria, Golgi system, endoplasmic reticulum and cytoplasmic granules; number of mitochondria per cell profile; number of cytoplasmic granules per cell profile and per micron2 of cytoplasm, as well as the azurophilic to specific granule ratio and mean diameter of granules. A significant decrease in cell profile area and cytoplasm profile area was shown in ethanol-treated rats. The volume density of mitochondria and endoplasmic reticulum nearly doubled during ethanol abuse. The results also showed that there were highly significant effects of ethanol on the total number of cytoplasmic granules per cell. In addition, changes were observed in mitochondria such as clumping, elongation, swelling and disruption of cristae, as well as changes in the topographic distribution of granules in the cytoplasm such as registration of cytoplasmic areas with numerous granules and areas with a smaller number or without any granules. Some neutrophils of ethanol-treated rats had autophagic vacuoles. The results indicate some ultrastructural abnormalities of PMN in chronic experimental alcoholism that may be related to polymorphonuclear phagocyte dysfunction.

Effects of chronic ethanol administration on the serotonin-producing cells in rat gastric antral and duodenal mucosa.

The present study describes our observations on optical and ultrastructural features of serotonin-containing cells in the rat antral and upper duodenal mucosa, utilizing optic morphometric measurements in a model of experimental chronic alcoholism of rat in which nutrition was well controlled. Male Wistar rats were given ethanol to provide 23 per cent of the total calories, while starch replaced ethanol isocalorically in controls. Twenty-five per cent of the calories were provided by protein in both groups. Blood levels of serotonin were significantly raised after chronic ethanol feeding (0.059 +/- 0.06 vs. 0.159 +/- 0.012 micrograms/ml, p < 0.01). Decrease in the number of immunohistochemically-detectable serotonin-containing cells was found in the pyloric gland mucosal area specimens of the chronically ethanol-treated rats (68.9 +/- 5.2 vs 43.3 +/- 3.0; p < 0.001). The immunohistologically-evaluated number of the same cells in the duodenal mucosa specimens was significantly decreased by alcohol feeding. Although total villi and crypt count per whole circular section, and the number of crypts per villus were not significantly changed either in control animals or in chronically ethanol-fed rats, decreased number of these cells per whole circular section (289 +/- 21.6 vs. 183 +/- 10.5; p < 0.001) per villus (2.52 +/- 0.14 vs. 1.21 +/- 0.10; p < 0.001) and per crypts (0.97 +/- 0.08 vs. 0.79 +/- 0.04; p < 0.05) were reported after alcohol consumption. In both control and experimental rats the cells were predominantly found in the basal half of the antropyloric mucosa. Alcohol did not lead to any changes in normal distribution of the duodenal serotonin-producing cells. The above quantitative changes in serotonin-producing cells were not accompanied by changes in their subcellular appearance in stomach and duodenal mucosa of alcohol-treated rat.