Long-term effect of losartan administration on blood pressure, heart and structure of coronary artery of young spontaneously hypertensive rats

Alterations in geometry and structure of coronary arteries have marked consequences on blood flow to the respective area. We evaluated long-term effect of losartan on blood pressure (BP), heart weight/body weight (HW/BW), geometry and structure of septal branch of coronary artery (RS) of young SHR and Wistar rats. Four-week-old Wistar rats and SHR were used. Losartan was administered (20 mg/kg/day) in drinking water by gavage for 5 weeks. BP was measured by plethysmographic method. Cardiovascular system was perfused with a fixative (120 mm Hg). RS was processed for electron microscopy. Wall thickness of intima + media (WT), inner diameter (ID), cross-sectional area of intima + media (CSA), volume densities (VD) of endothelial cells (EC), extracellular matrix (ECM) of intima, smooth muscle cells (SMC) and ECM of media were evaluated. BP of 4-week-old SHR did not differ from that of Wistar rats. BP, HW/BW, WT, CSA, WT/ID, CSAs of SMC, ECM of media were increased in 9-week-old SHR, whereas their VD and CSA of EC were decreased. Losartan administration decreased BP and HW/BW in both groups. Geometry of RS was affected only in SHR (reduction of WT, CSA, WT/ID and increased of ID, circumferential tension, VD and CSA of EC). Losartan administration reduced BP and myocardial mass in both groups and beneficially affected geometry and structure of coronary artery in SHR.     

Differential remodeling of carotid artery in spontaneously hypertensive and hereditary hypertriglyceridemic rats

High blood pressure, increased level of cholesterol, diabetes, hypertriglyceridemia and obesity are risk factors accompanied metabolic syndrome. The aim of the study was to compare geometry of carotid artery (AC) of 3-week-old (3w) and 52-week-old (52w) hereditary hypertriglyceridemic rats (hHTG) and spontaneously hypertensive rats (SHR) which represent a genetic model of human essential hypertension with age-matched Wistar rats. After sacrificing the rats were perfused with a glutaraldehyde fixative under the pressure 90 mm Hg (3w) and 120 mm Hg (52w) for 10 min via cannula placed into left ventricle. Middle part of AC was excised and processed according to standard electron microscopy procedure. Geometry of AC was evaluated in light microscopy. SHR vs. Wistar rats: BP of 3w did not differ, in 52w it was increased; cardiac hypertrophy was found in both ages; wall thickness (WT) and cross sectional area (CSA) in 3w did not differ, in 52w both were increased; inner diameter (ID) in 3w and 52w was decreased; WT/ID was increased in both ages. Hereditary HTG vs. Wistar rats: BP was increased in both periods; cardiac hypertrophy was observed in 3w; WT in 3w was decreased, in 52w it was increased; CSA and ID were decreased in both ages; WT/ID was increased only in 52w. Discrepancies between development of BP, cardiac hypertrophy in SHR and hHTG rats were observed. Alterations of BP were not in harmony with alterations in geometry of carotid arteries in both SHR and hHTG rats. We suggest that BP is not the main stimuli evoked hemodynamic and structural alterations of cardiovascular system in ontogenic development of SHR and hHTG rats.     

Long-term effect of prazosin administration on blood pressure, heart and structure of coronary artery of young spontaneously hypertensive rats

The sympathetic nervous system belongs to the essential systems participating in blood pressure (BP) regulation. Inhibitory intervention into the key point of its operation (alfa 1 adrenoceptors) in the prehypertensive period of spontaneously hypertensive rats (SHR) might affect the development of the hypertension in later ontogenic periods. We studied the long-term effect of prazosin administration on the cardiovascular system of young Wistar rats and SHR. Four-week-old animals were used: Wistar rats, SHR, and Wistar rats and SHR receiving prazosin (10 mg/kg/day in tap water) by gavage. Blood pressure (BP) was measured weekly by the plethysmographic method. After six weeks under anaesthesia, the carotid artery was cannulated for BP registration, and the jugular vein was cannulated for administration of drugs. Afterwards, the animals were perfused with a glutaraldehyde fixative at a pressure of 120 mmHg. The septal branch of the left descending coronary artery was processed using electron microscopy. The prazosin administration evoked the following results in both groups: a decrease of BP and heart/body weight ratio, enhancement of hypotensive responses to acetylcholine (0.1 μg, 1 μg, and 10 μg), and an increase in the inner diameter of the coronary artery without changes in wall thickness, cross sectional area (CSA) (tunica intima+media), CSA of smooth muscle cells, and extracellular matrix. In the SHR group, a reduction was observed in BP increase after noradrenaline (1 μg) application. CSA of endothelial cells which was decreased in the SHR (compared to the control Wistar rats) was increased after prazosin treatment (up to control value). Long-term prazosin administration from early ontogeny partially prevented some pathological alterations in the cardiovascular system of SHR.     

Increased medial smooth muscle cell length is responsible for vascular hypertrophy in young hypertensive rats

Large mesenteric arteries from 3- to 4-wk-old spontaneously hypertensive rats (SHR) showed medial hypertrophy and an increased contractile response to various agonists before significant blood pressure increase. Here we determined the cellular nature of this vascular hypertrophy. Large mesenteric arteries from SHR and Wistar-Kyoto (WKY) rats were fixed at maximal relaxation either with an in situ perfusion fixation or an in vitro fixation method. With the use of morphometric protocols and confocal microscopy, the volume of the medial wall and lumen, numerical density of smooth muscle cell nuclei in the medial layer, and smooth muscle cell and nuclear length were measured. Both methods of fixation yielded similar results, showing significant medial volume expansion in SHR than WKY without lumen change. Numerical density of medial smooth muscle cells was significantly less in SHR than WKY, and their total number per 100 microm length were similar between the strains. Average smooth muscle nuclear and cell length from SHR was significantly longer than that of WKY. Regression analysis showed that the increase in smooth muscle cell length explained 80% of the medial volume increase. We concluded that increased smooth muscle cell length in prehypertensive SHR is responsible for increased medial volume in the mesenteric arteries.     

Integrative pattern of vasomotor efficiency in SHR during ontogenesis

Numerous studies concerning the cardiovascular system in SHR often yield controversial data. The background of this diversity has various roots, ranging from different vascular segments or areas studied up to the different age of experimental animals. Our study aimed to follow the BP as an integrated response of vascular system. This approach was justified since stabilized cardiac output in SHR was proved till 1 year of age. The groups of male SHR (aged 3, 5, 9, 17 and 52 weeks) and age-matched Wistar rats were used. Significant basal BP difference between SHR and Wistar rats was found at 9 weeks of age and continued till the age of 52 weeks, reaching 189.6+/-11.9 mm Hg in SHR and 117.3+/-6.9 mm Hg in Wistar rats P<0.01 . The significant difference in BP increase to two doses of noradrenaline 0.1 microg and 1 microg between SHR and control rats was also found at the age of 9 weeks. At 52 weeks the BP increment to two doses of noradrenaline was in SHR 19.7+/-2.0 mm Hg and 60.5+/-3.9 mm Hg and in Wistar rats 7.4+/-1.9 mm Hg and 40.5+/-3.2 mm Hg P<0.01 . The hypotensive response to acetylcholine 0.1 microg, 1 microg and 10 microg in SHR was enhanced at 17 weeks of age only and this amplification persisted till the age of 52 weeks. In 52-week-old SHR the hypotensive response to three doses was 69.9+/-10.2 mm Hg, 87.5+/-11.8 mm Hg and 103.4+/-10.6 mm Hg, while in Wistar rats it was 37.4+/-4.2 mm Hg P<0.01 , 62.3+/-3.5 mm Hg P<0.01 and 73.5+/-2.8 mm Hg P<0.05 . In conclusion, the efficiency of cardiovascular system of SHR to respond to noradrenaline was already enhanced from 9 weeks of age, whereas the response to acetylcholine was not augmented before the age of 17 weeks.     

Age-related alterations in epicardial arteries of spontaneously hypertensive rats

Proximal portions of the left coronary arteries were examined microscopically in aging female normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). The age-related intimal alterations in SHR were largely limited to endothelial cells, which demonstrated a proliferation of organelles (most notably Weibel-Palade bodies). In the media, degenerative alterations appeared to be most marked near the medio-adventitial junction. Compared to WKY and increasing with age, the media of the SHR epicardial artery demonstrated an accumulation of extracellular elements that included basement membrane-like material, collagen fibers and debris. Complex carbohydrates, as determined with the silver methenamine reaction, were noted to accumulate in a lamellar fashion. Smooth muscle cells demonstrated an age-related tendency (which was exaggerated in SHR) toward development of invaginations and irregular profiles. These observations indicate that age-related structural alterations in epicardial arteries of SHR are progressive, and they support the concept that structural alterations in SHR coronary arteries may represent accelerated aging phenomena.     

Exercise training attenuates blood pressure elevation and adverse remodeling in the aorta of spontaneously hypertensive rats

OBJECTIVE: To observe the extracellular matrix modifications and quantify the structural alterations of the aortic wall in spontaneously hypertensive rats (SHR) submitted to an aerobic physical activity (PA) protocol. MATERIAL AND METHODS: Three groups of five rats each were studied: sedentary normotensive Wistar rats (SED-Wistar) and SHR (divided in SHR that underwent a 1 h/day 5 days/week PA for 20 weeks (EX-SHR) and those that were restricted to cage-bound activity (SED-SHR). RESULTS: BP was lower in EX-SHRs and SED-Wistar rats (-35%) than in SED-SHRs. This difference became significant from the 3rd week of PA. The wall thickness was smaller in the EX-SHR and SED-Wistar (-45%) than in the SED-SHR (p<0.0001). In EX-SHR group, oxytalan and elaunin fibers were more pronounced than in the other groups, while SED-SHR and SED-Wistar rats showed an equivalent appearance of aortic elaunin fibers. EX-SHR and SED-Wistar rats showed more than 65% greater smooth muscle nuclei numerical density per unit area than SED-SHRs while SED-SHRs showed more than 45% smaller surface density of lamellae than both EX-SHR and SED-Wistar rats. However, no quantitative differences were found in the aortic wall comparing EX-SHR and SED-Wistar rats. CONCLUSION: PA might alter the aortic wall remodeling to adapt the artery to a hyperkinetic blood flow resulting in alterations of the extracellular matrix modulation and vascular resistance.     

Decreased velocity of shortening in arterial smooth muscle from older (28- to 31-week-old) spontaneously hypertensive rats

An increased maximum velocity of shortening (Vmax) and increased shortening ability (delta Lmax) have been reported for caudal arterial smooth muscle from 16- to 18-week-old spontaneously hypertensive rats (SHR) compared with age-matched Wistar-Kyoto (WKY) control rats. It is known that hypertension results in hypertrophy of vascular smooth muscle. It is plausible that the faster Vmax of 16- to 18-week-old SHR arterial smooth muscle may slow down with age due to hypertrophy. The force-velocity (F-V) study done previously on caudal arterial strips from 16- to 18-week-old SHR and WKY rats was repeated on preparations from 28- to 31-week-old rats. An electromagnetic muscle lever was employed in recording force-velocity data. Analysis of these data revealed that the 28- to 31-week-old SHR (n = 7) mean F-V curve was not different from the 28- to 31-week-old WKY (n = 5) mean F-V curve (p greater than 0.05), and the shortening ability of 28- to 31-week-old SHR arterial muscle was significantly depressed compared with 28- to 31-week-old WKY arterial muscle (p less than 0.01). In conclusion, (i) although Vmax is faster in younger (16- to 18-week-old) SHR compared with age-matched WKY caudal arterial smooth muscle, SHR Vmax is not different from WKY Vmax in the older (28- to 31-week-old) rats. (ii) Shortening ability is greater in 16- to 18-week-old SHR caudal arterial strips compared with 16- to 18-week-old WKY strips, but is significantly depressed in 28- to 31-week-old SHR compared with 28- to 31-week-old WKY preparations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of vascular function and structure of iliac artery in spontaneously hypertensive and hereditary hypertriglyceridemic rats

The aim of this study was to compare the vascular reactivity and morphology of iliac artery (IA) in adult spontaneously hypertensive rats (SHR) and hereditary hypertriglyceridemic (hHTG) rats. The isolated rings of iliac artery (IA) from Wistar rats (controls), SHR and hHTG rats were used for measurement of relaxant responses to acetylcholine (ACh) and contractile responses to noradrenaline (NA). Morphological changes of IA were measured using light microscopy. Systolic blood pressure (BP) measured by plethysmographic method was increased in SHR approximately by 88 % and in hHTG rats by 44 % compared to controls. BP increase was accompanied by cardiac hypertrophy. In both SHR and hHTG groups (experimental groups) reduced relaxation to ACh and enhanced maximal contraction and sensitivity to adrenergic stimuli were observed. The sensitivity to NA in SHR was higher also in comparison with hHTG. Geometry of IA in both experimental groups revealed increased wall thickness and wall cross-sectional area, in SHR even in comparison with hHTG. Inner diameter was decreased in both experimental groups. Thus, independently of etiology, hypertension in both models was connected with impaired endothelial function accompanied by structural alterations of IA. A degree of BP elevation was associated with arterial wall hypertrophy and increased contractile sensitivity.     

Chloride channel activity of vascular smooth muscle in the spontaneous hypertensive rats

To characterize the activity of the Ca2+-activated Cl- channels in vascular smooth muscle (VSM) of the spontaneous hypertensive rats (SHR), the isolated mesenteric vascular beds and tail artery strips were preparated from SHR and Wistar rats aged 7-8 weeks. The changes in contractile response to norepinphrine (NE) were taken as an index of vascular mortion. Results showed that the contractile responses of mesenteric arteries and tail arteries to NE in SHR were significantly greater than that in Wistar rats. The inhibition magnitude of the contractile response by Ca2+-activated Cl- channel blocker, niflumic acid in SHR was significantly less than that in Wistar rats. Decreasing the extracellular Cl- concentration increased the contractile response to NE significantly, but the amplitude of enhanced contractile response in SHR was greater than that in Wistar rats. It can be concluded that NE-induced contraction was enhanced in SHR, which is partly due to an increase in Cl- efflux through the Ca2+-activated Cl- channels. The chloride channel activity may be increased in association with the elevation of blood pressure.     

Long-term effects of early administered sildenafil and NO donor on the cardiovascular system of SHR.

We evaluated the long-term effect of NO-donor, pentaerythrityl tetranitrate (Petn), and sildenafil citrate (sildenafil) on the cardiovascular system of the spontaneously hypertensive rat (SHR). Petn (100 mg/kg/day) and sildenafil (10 mg/kg/day) were administered to SHR individually or together from week 4 (pre-hypertensive period) to week 9 of age. Blood pressure (BP) was measured using a plethysmographic method. The animals were perfused with a glutaraldehyde fixative (120 mmHg). Carotid (AC) and coronary artery (RS) were processed according to electron microscopy procedure. Geometry of the arteries was measured on semi-thin sections using light microscopy. Administration of Petn and sildenafil to SHR individually or together did not prevent an increase of BP, but evoked a decrease of cardiac hypertrophy. Petn and sildenafil affected the geometry of RS and AC differently. In the RS, an increase of inner diameter (ID) without an increase of wall thickness (WT) resulted in increased WT/ID and circumferential stress. In the AC, changes in ID were accompanied by changes in WT and, thereby, WT/ID and circumferential stress remained unchanged. The arterial wall mass of both arteries was increased. The data suggest that administration of the NO donor, Petn, and/or sildenafil does not result in a beneficial effect on the myocardium or on the geometry of the carotid and coronary arteries.     

Matrix Gla protein accumulates at the border of regions of calcification and normal tissue in the media of the arterial vessel wall.

Vitamin K-dependent matrix Gla protein (MGP) has been suggested to play a role in the inhibition of soft-tissue calcification. Here we report the expression of recombinant prokaryotic MGP as part of a fusion protein and the preparation of two antibodies that specifically recognize MGP. Monoclonal antibodies were raised against synthetic peptides homologous to the sequences 3-15 and 63-75 of human MGP. Both antibodies recognize recombinant and synthetic human MGP. Immunohistochemical analysis showed that MGP was associated with the extracellular matrix of noncalcified bone and with chondrocytes in cartilage. In the healthy human arterial vessel wall, MGP antigen was demonstrated in association with smooth muscle cells and elastic laminae of the tunica media and with the extracellular matrix of the adventitia. Colocalization with the elastic laminae was lost at sites of medial calcification; in both human and rat arteries, high amounts of MGP were found in the extracellular matrix at borders of intimal and medial calcification. Our data demonstrate the close association between MGP and calcification. It is suggested that undercarboxylated MGP is biologically inactive and that poor vascular vitamin K status may form a risk factor for vascular calcification.     

The relationship between altered blood vessel structure, hypertension, and the sympathetic nervous system

The relationship between sympathetic innervation and arterial medial development has been examined in normotensive, hypertensive, and diabetic rats. Using the jejunal artery as a model, the number of nerve fibres innervating the artery as determined from fluorescent preparations, and the medial thickness and lumen diameter as measured from resin embedded specimens were correlated from animals prepared in various ways. The rats used were normal Sprague-Dawley (SD), SD with induced hypertension, SD with diabetes induced with streptozotocin, SD sympathectomized with 6-hydroxydopamine, spontaneously hypertensive rats (SHR), SHR treated with capsaicin to prevent hypertension development, Wistar Kyoto rats (WKY), and WKY treated with capsaicin. Examination of the jejunal arteries from these rats at 12 weeks of age following normal development, or 8 weeks of hypertension development, or 8 and 12 weeks of diabetes, showed that increased innervation occurred in the SHR under all conditions, and in the diabetic rats after 8 weeks of diabetes. Medial hypertrophy occurred in the SHR and in the SD hypertensive only. It is concluded that the special relationship which exists between the sympathetic innervation and arterial media in the SHR does not occur during hypertension development in the SD rat, nor is it necessary for normal medial development in the SD rat. The sympathetic innervation does appear to have a trophic influence on vascular smooth muscle of diabetic rats, at least in the early stages of the disease.     

Studies of arterial smooth muscle relaxation in younger (16-18 week) and older (28-31 week) spontaneously hypertensive rats

Both isometric and isotonic relaxation rates have previously been reported to be decreased in caudal arterial and mesenteric resistance arterial smooth muscle from 16- to 21-week-old spontaneously hypertensive rats (SHR) compared with muscle from age-matched normotensive Wistar-Kyoto rats (WKY). An increased maximum velocity of shortening (Vmax) and an increased shortening ability (delta Lmax) have also been reported for arterial smooth muscle from 16- to 21-week-old SHR. It has been suggested that both increased narrowing and prolonged narrowing of arteries contribute to the development of hypertension. However, SHR Vmax is not different from WKY Vmax when studying arterial muscle from older (28- to 31-week-old) rats. Thus increased arterial narrowing ability cannot be a contributing factor to the maintenance of hypertension. In this study the role of relaxation rate in the maintenance of hypertension was examined by comparing the relaxation rates of isometric and isotonic contractions of caudal arterial strips from 16- to 21-week-old SHR (n = 9) and WKY (n = 8) and from 28- to 31-week-old SHR (n = 7) and WKY (n = 5). While relaxation rates were lower for 16- to 21-week-old SHR compared with age-matched WKY preparations for both isometric and isotonic contractions, only isometric relaxation rates were found to be different in 28- to 31-week-old SHR compared with 28- to 31-week-old caudal arterial muscle (p less than 0.05). Vmax tended to normalize from a once-elevated velocity, while isometric relaxation rate remained decreased in SHR with ageing and (or) with progression of the hypertensive condition.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of hindlimb unloading on rat cerebral, splenic, and mesenteric resistance artery morphology.

Hindlimb unloading (HU) of rats induces a cephalic shift in body fluids. We hypothesized that the putative increase in cranial fluid pressure and decrease in peripheral fluid pressure would alter the morphology of resistance arteries from 2-wk HU male Sprague-Dawley rats. To test this hypothesis, the cerebral basilar, mesenteric, and splenic arteries were removed from control (C) and HU animals. The vessels were cannulated, and luminal pressure was set to 60 cmH(2)O. The resistance arteries were then relaxed with 10(-4) M nitroprusside, fixed, and cut into transverse cross sections (5 microm thick). Media cross-sectional area (CSA), intraluminal CSA, media layer thickness, vessel outer perimeter, and media nuclei number were determined. In the basilar artery, both media CSA (HU 17, 893 +/- 2,539 microm(2); C 12,904 +/- 1,433 microm(2)) and thickness (HU 33.9 +/- 4.1 microm; C 22.3 +/- 3.2 microm) were increased with hindlimb unloading (P < 0.05), intraluminal CSA decreased (HU 7,816 +/- 3,045 microm(2); C 13,469 +/- 5,500 microm(2)) (P < 0.05), and vessel outer perimeter and media nuclei number were unaltered. There were no differences in mesenteric or splenic resistance artery morphology between HU and C rats. These findings suggest that hindlimb unloading-induced increases in cephalic arterial pressure and, correspondingly, increases in circumferential wall stress result in the hypertrophy of basilar artery smooth muscle cells.     

Inhibition by cinnarizine of the responses of smooth muscle from spontaneously hypertensive and normotensive rats

A comparison was made of the inhibition by cinnarizine, a calcium antagonist, of the contractile responses of aortic, carotid, and iliac arterial strips and vasa deferentia from 15- to 17-week-old spontaneously hypertensive rats (SHR) and their normotensive counterparts, Wistar Kyoto (WKY) rats. KCl-induced responses of the aorta from both strains of rats and carotid arteries from WKY only were more sensitive to inhibition than were responses to norepinephrine. No significant differences were observed in the inhibition of tissue responses from the two strains of rats with the exception of the K+-induced responses of carotid arterial strips from SHR which were significantly less sensitive to inhibition when compared with carotid strips from WKY.     

Chronic all-trans retinoic acid treatment prevents medial thickening of intramyocardial and intrarenal arteries in spontaneously hypertensive rats

There are in vitro data linking all-trans retinoic acid (atRA) with inhibition of hypertrophy and hyperplasia in cardiomyocytes, vascular smooth muscle cells, and fibroblasts. In the present study, we tested the hypothesis that chronic treatment with atRA may blunt the process of myocardial remodeling in spontaneously hypertensive rats (SHR). Four-week-old male SHR were treated with atRA (5 or 10 mg.kg-1.day-1) given daily for 3 mo by gavage; age- and sex-matched Wistar-Kyoto rats (WKY) and placebo-treated SHR served as controls. At the end of the treatment period, cardiac geometry and function were assessed by Doppler echocardiography. Histological examination and RIA were performed to evaluate medial thickening of intramyocardial and renal arteries, perivascular and interstitial collagen content, and atrial natriuretic peptide (ANP) and IGF-I in the heart, respectively. The novel finding of the present study is that atRA prevented hypertrophy of intramyocardial and intrarenal arteries and ventricular fibrosis. However, atRA treatment did not lower blood pressure or left ventricular weight and left ventricular weight-to-body weight ratio in SHR. atRA did not change cardiac geometry and function as assessed by Doppler echocardiography. atRA showed no influence on either ANP or IGF-I levels. In conclusion, the present study suggests that chronic atRA treatment prevents medial thickening of intramyocardial and intrarenal arteries and ventricular fibrosis during the development of hypertension. Left ventricular hypertrophy and cardiac geometry and function are not changed by atRA treatment.     

Isolation of a morphologically and functionally distinct smooth muscle cell type from the intimal aspect of the normal rat aorta. Evidence for smooth muscle cell heterogeneity

Summary Recent studies indicate that the neointima of injured rat arteries is composed of a subpopulation of smooth muscle cells (SMCs) distinct from medial smooth muscle cells. However, SMC diversity in normal adult aorta has remained elusive. This study characterizes two morphologically and functionally distinct SMC types isolated from different anatomic regions of the normal rat aorta. Rat aortic medial smooth muscle cells (MSMCs) were isolated from the media after removal of the intimal and adventitial cells. Rat aortic intimal smooth muscle cells (ISMCs) were isolated from the intimal aspect of everted rat aortas. The two cell types were characterized morphologically and immunohistochemically and were compared for their capacity to contract collagen gels in response to endothelin-1. MSMCs were spindle-shaped and grew in hills and valleys showing features previously described for vascular SMCs. Conversely, ISMCs displayed a polygonal and epithelioid shape, grew mainly as a monolayer, and had a higher proliferative rate. Both cell types expressed alpha-smooth muscle actin and were negative for Factor VIII-RAg. ISMCs produced large amounts of a laminin and type IV collagen-rich extracellular matrix which had a characteristic pericellular distribution. ISMCs, but not MSMCs, rapidly contracted collagen gels in response to endothelin-1. This study indicates that the normal rat aorta contains two types of SMCs located in anatomically distinct regions of the vessel wall. Because of their functional characteristics, the SMCs isolated from the intimal aspect of the aorta may play an important role in physiologic as well as pathologic conditions.     

Early recovery from hypoxic pulmonary hypertension: a structural and functional study

This study follows the recovery during 1 mo in ambient air from the hemodynamic and structural changes found in Sprague-Dawley rats after 2 wk of hypobaric hypoxia. In the time studied there is some degree of recovery for all features analyzed. The only features that completely return to normal are hematocrit level, new muscle in arteries at alveolar wall level, medial thickness of intra-acinar arteries, and density of filled arteries. For some features much of the recovery is early or rapid; for other features the recovery is late or slow. The rapid changes, occurring within two days of removal from hypoxia, include a fall in pulmonary arterial pressure (36.6 +/- 1.5 to 30.1 +/- 1.1 mmHg), a drop in hematocrit (61.1 +/- 1.3 to 53.0 +/- 1.0%), and the disappearance of new muscle, as judged by light microscopy from many arteries at alveolar wall (39.5 +/- 4.9 to 17.7 +/- 4.0%) and alveolar duct (85.9 +/- 2.5 to 68.2 +/- 3.4%) levels. The slow recovery includes the decrease in right ventricular and arterial medial hypertrophy, disappearance of muscle from respiratory bronchiolar arteries, reduction in lung volume, and increased density of filled arteries. These slow changes are probably the response to a fall in pulmonary arterial pressure.     

Effects of long-term treatment with captopril on the isomyosin profile of the heart from SHR and Wistar rats

Heart myosin isoforms and arterial blood pressure changes were studied in 30 SHR rats following a long-term treatment with captopril. 30 Wistar rats were included in the same trial as control. Twelve week old SHR rats with an already established hypertension and ventricular hypertrophy were orally administered with between 25 and 100 mg/Kg/die of captopril. After a ten-week treatment, animals were sacrificed and heart myosin isoforms (V1, V2, V3) analysed by polyacrylamide gel electrophoresis. Our results showed that captopril can: a) reduce blood pressure; b) reduce the cardiac hypertrophy; c) reverse the isomyosin enzymes (V1 V3) previously altered by the hypertrophy condition (V3 V1) to normal value. Furthermore we have detected an increase of V myosin isoform in SHR rats (35%) and to a lower extent in treated Wistar rats (17%). Since SHR and Wistar rats usually do not express V isoform, our results suggest that captopril may be responsible for this phenomenon by acting directly on myocardial cells.