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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The contractile activity of the hypertrophied myocardium was investigated in Langendorff perfused hearts from one-kidney one-clip (1K1C) renovascular hypertensive rats. 2. Hearts obtained from control and renovascular hypertensive animals were studied 15, 30 and 60 days after sham operation (SO) or renovascular hypertension induction. Rats were anesthetized with ether and mean blood pressure (MBP) and heart rate (HR) were measured. The hearts were then excised and perfused with Krebs solution and bicarbonate buffer, at 31 degrees C, with a perfusion pressure of 75 mmHg, beating spontaneously. The left ventricular function curves were evaluated by measuring the isovolumic systolic pressure (ISP) obtained at diastolic pressures (DP) of 0, 10, 20 and 30 mmHg in 0.62, 1.25 and 2.5 mM extracellular calcium. After the experiments the left ventricle (LV) was dissected, blotted and dried to obtain the dry and wet weights. 3. The 1K1C animals were hypertensive and displayed LV hypertrophy. The LV function curves showed the expected behavior, being similar for all 3 calcium concentrations used for the 15-day groups. However, at 30 days, ISPs were lower than those from the SO control group. Moreover, after 60 days ISPs from 1K1C rat ventricles were higher than controls in 0.62 mM calcium for all DPs. For all other DPs, ISP from 1K1C and control ventricles were similar. Normalization of ISP to LV dry weight showed that the hypertrophied ventricles, at any time and at all calcium concentrations used, developed less pressure by ventricular mass than SO controls. 4. Absolute ISP results suggest changes in the contractile machinery characteristics, not only as a function of the pressure overload but also as a function of the hypertension time course, and that ISP normalization to ventricular mass demonstrated the lower capacity of the hypertrophied muscle to generate force and pressure.
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PMID:Time-dependent changes of left ventricular contractility in Langendorff perfused hearts from renovascular hypertensive rats. 808 5

We studied functional and intracellular calcium responses to treppe and extracellular calcium in spontaneously hypertensive rat (SHR) hearts during the transition from compensated pressure overload to failure. Intracellular calcium was measured using aequorin, a bioluminescent Ca2+ indicator. Experiments were performed with intact, isovolumically contracting, buffer-perfused hearts from three rat groups: (1) aging SHR with evidence of heart failure (SHR-F), (2) age-matched SHR with no evidence of heart failure (SHR-NF), and (3) age-matched normotensive Wistar-Kyoto (WKY) rats. In each experiment, left ventricular pressure and intracellular calcium transients were simultaneously recorded. Hearts were studied at 30 degrees C and paced at a rate of 1.6 Hz while being perfused with oxygenated Krebs-Henseleit solution (95% O2/5% CO2) at 100 mm Hg. At the baseline state, peak systolic pressure was greatest in the SHR-NF group and lowest in the SHR-F group. Peak and resting [Ca2+]i were not significantly different among groups; however, the calcium transient was prolonged in the SHR-NF and SHR-F groups. With increasing perfusate [Ca2+]o from 0.5 to 3.0 mmol/L, the relative increases in peak [Ca2+]i and peak systolic pressure were similar among groups. When stimulation rate was increased from 1.6 to 2.0, 2.4, 2.8, and 3.2 Hz, peak [Ca2+]i, peak systolic pressure, and +/- dP/dt fell in SHR-F hearts. Peak systolic pressure decreased in the SHR-NF group at rates above 2.4 Hz but did not decline in the WKY group. Peak [Ca2+]i increased in the WKY and SHR-NF groups with increasing heart rates. Peak systolic pressure did not fall significantly in the WKY group at any heart rate. Elevation of diastolic [Ca2+]i and/or calcium transient and pressure alternans were present in 8 of 13 SHR-F hearts at the highest stimulation rate, findings that were absent in both the WKY and SHR-NF hearts. We conclude the following: (1) Under baseline conditions, depressed contractile function of failing myocardium cannot be explained by decreased peak [Ca2+]i, (2) relative increases in [Ca2+]i and inotropy with increasing [Ca2+]o are proportional among groups; and (3) although peak systolic [Ca2+]i and inotropy are maintained with increasing stimulation rate in the WKY and SHR-NF groups, peak systolic [Ca2+]i and pressure decrease in parallel in the SHR-F heart with increasing stimulation rate, suggesting that impaired calcium cycling may contribute to compromised pump function in the SHR-F heart.
Hypertension 1994 Sep
PMID:Effects of treppe and calcium on intracellular calcium and function in the failing heart from the spontaneously hypertensive rat. 808 41

In both humans and experimental animals, mineralocorticoid (MC)-induced hypertension is associated with myocardial fibrosis. We have shown that this fibrous tissue response includes a reactive interstitial fibrosis not initiated by parenchymal cell loss, and a reparative fibrosis or scarring, occurring in response to cardiac myocyte necrosis. The reactive fibrosis is thought to be related to MC excess, while cell loss and microscopic scarring may be secondary to enhanced potassium excretion or a cytotoxic effect of aldosterone. This histologic study was undertaken to determine whether or not the potassium sparing diuretic amiloride would be effective in preventing the appearance of either form of fibrosis. Uninephrectomized male Sprague Dawley rats received either aldosterone (AL; 0.75 microgram/h), amiloride (AMC; 1 mg/kg/day), aldosterone+amiloride (ALAM), or vehicle (ALC) alone via subcutaneous osmotic minipumps for 8 weeks. All rats received 1% NaCl in their drinking water. Hearts were recovered, immersion-fixed, and tissue sections from both left and right ventricles stained with the collagen specific stain Sirius Red F3BA were morphometrically analyzed. The interstitial collagen volume fraction was elevated in AL and ALAM groups compared to ALC and AMC, but did not differ between AL and ALAM. Microscopic scarring, found in both ventricles, was evident in AL animals, but was not found in the ALAM, AMC, or ALC groups. These data suggest that chronic elevations in plasma aldosterone, relative to dietary sodium intake, do not have a direct cytotoxic effect on cardiac myocytes, but they are associated with a reactive interstitial fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myocardial fibrosis in the rat with mineralocorticoid excess. Prevention of scarring by amiloride. 834 31

Left ventricular isovolumic stress development and metabolic parameters were studied in 18-24-month-old spontaneously hypertensive rats (SHRs) and age-matched Wistar-Kyoto (WKY) rat controls using the isolated, isovolumic (balloon in left ventricle) buffer-perfused rat heart preparation. After WKY rats and all SHRs were compared, SHRs were divided into two groups: those animals with (SHR-F) and without (SHR-NF) evidence of heart failure. Hearts were perfused at 100 mm Hg using a constant pressure system at a temperature of 37 degrees C. In the baseline state, peak systolic pressure was greatest in the SHR-NF group and lowest in the SHR-F group. Peak midwall stress was greatest in the WKY group and, again, lowest in the SHR-F group. Oxygen consumption was lowest in the SHR-F group. When the oxygen cost of stress development was estimated by normalizing myocardial oxygen consumption by peak developed midwall stress, values were lowest in the WKY, greater in the SHR-NF, and greatest in the SHR-F group. Lactate production did not occur in the baseline state in any of the groups. Functional and metabolic responses to graded hypoxia, induced by changing the gas mixture of the perfusate from 95% to 50%, 25%, and 0% oxygen at perfusion pressures of 100 and 130 mm Hg, were studied. Increasing perfusion pressure generally resulted in small increases in peak systolic pressure and myocardial oxygen consumption but did not substantially reverse the contractile or metabolic deficit present in the SHR-F group.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1993 Jan
PMID:Oxygen cost of stress development in hypertrophied and failing hearts from the spontaneously hypertensive rat. 841 24

Angiotensin-converting enzyme inhibitors reduce blood pressure and cardiac mass but may also have a direct effect on myocardial growth. To test this hypothesis, we studied the effects of perindopril on the weight of transplanted hearts in which the left ventricle does not pump blood. Hearts were transplanted between littermate 10-week-old male spontaneously hypertensive rats, and recipients were treated for 2 weeks with vehicle (n = 10), perindopril (3 mg/kg per day) (n = 9), perindopril (3 mg/kg per day) plus the selective bradykinin B2 receptor antagonist Hoe 140 (500 micrograms/kg per day) (n = 13), or angiotensin II (200 ng/kg per minute) (n = 12). Perindopril reduced blood pressure and native left ventricular weight and also caused a significant decrease in the weight of the transplanted left ventricle compared with controls. Hoe 140 did not significantly alter blood pressure or native left ventricular weight of perindopril-treated rats but caused a significant increase in the weight of the transplanted left ventricle compared with rats treated with perindopril alone. Angiotensin treatment resulted in a significant increase in blood pressure and native left ventricular weight but no significant change in the weight of the transplanted left ventricle. Blood pressure and left ventricular weight for native but not for transplanted hearts were positively correlated. Therefore, in the absence of mechanical load, the weight of the left ventricle of spontaneously hypertensive rats responds little to angiotensin II but can be reduced by angiotensin-converting enzyme inhibition. The effect of perindopril on transplanted hearts of spontaneously hypertensive rats appears to depend on bradykinin.
Hypertension 1996 Oct
PMID:Cardiac transplantation, perindopril, and left ventricular hypertrophy in spontaneously hypertensive rats. 884 88

The renin-angiotensin system has been implicated in the hypertrophic adaptation of the heart to exogenous pathological loads, such as hypertension and aortic stenosis; however, the role of this hormonal system in the cardiac adaptations to physiological loads, such as chronic exercise conditioning, has not been established. We therefore studied the effect of angiotensin receptor 1 (AT1) blockade on the chronic cardiac responses of rats subjected to an 8-wk swimming program. Compared with matched sedentary controls, untreated swimmers increased their left ventricular weights by 13%, and swimmers treated with the AT1 antagonist L-158809 increased their left ventricular weights by 11% (both P < 0.05 vs. sedentary controls). The incorporation of labeled amino acids into the heart at the time of death was unchanged in all groups, and therefore the increase in heart weight in both swim-conditioned groups appeared to reflect a decrease in the rate of protein degradation in the heart. Hearts from both swim-conditioned groups manifested an increase in the V1-predominant myosin isoform pattern but not an increase in atrial natriuretic factor mRNA expression or protein kinase C translocation. The fact that these patterns of adaptation are preserved in exercised conditioned animals treated with an AT1 antagonist suggests that the chronic hypertrophic response of the heart to physiological loads is not influenced by the renin-angiotensin system.
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PMID:Angiotensin receptor 1 blockade does not prevent physiological cardiac hypertrophy in the adult rat. 887 51

Pathophysiological effects of nitric oxide (NO)-deficient hypertension are much better known than are the potential morphological changes. Hearts and main arteries were studied in 15 week old male Wistar rats administered NG-nitro-L-arginine methyl ester (L-NAME) for 4 weeks. A does of 40 mg/kg/day increased systolic arterial pressure by 30%, while heart rate decreased by 20%. Heart/body weight ratios were not significantly changed. Total cardiac RNA and DNA content and [14C]leucine incorporation into myocardial protein were, however, increased by 15%, 228% and 97%, respectively. Light microscopy of hearts showed subendocardial areas of necrosis along with different stages of healing. Morphometric evaluation demonstrated significant increase in myocardial fibrosis. Serum lactate dehydrogenase increased by 91%. Proliferation cell nuclear antigen (PCNA) immunohistochemistry indicated positive cells in areas of postischemic repair. Chronic inhibition of NO synthase (NOS) resulted in periarterial fibrosis and hyperplasia of the media in coronary arteries and aorta. RNA and DNA content, and [14C]leucine incorporation into protein of aorta increased by 255%, 95% and 49%, respectively. PCNA staining showed numerous positive nuclei in the media of coronary arteries and the aorta. It is concluded that inhibition of NOS leads to systemic hypertension with focal myocardial fibrosis reflecting reparative responses associated to ischemic injury. This sequence of alterations involves impaired arterial relaxation, and uncontrolled vascular medial proliferation attributed to the absence of smooth muscle cell proliferation inhibition by NO.
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PMID:Chronic inhibition of NO synthesis produces myocardial fibrosis and arterial media hyperplasia. 922 43

1. Recent evidence suggests that nitric oxide (NO) modulates the contractile force of isolated cardiomyocytes in a biphasic manner. We sought to examine whether myocardial hypertrophy induced by long-term hypertension changes the effects of NO on myocardial contractility. 2. We used constant flow perfused non-paced Langendorff preparations of hearts of 3 months old Wistar rats (WIS, n = 23) and of stroke-prone spontaneously hypertensive rats (SHR) at the age of 10 months (SHR10, n = 16) and 15 months (SHR15, n = 8). Changes of left ventricular peak pressure (LVP), +dP/dt(max), -dP/dt(max), coronary perfusion pressure (CPP) and heart rate (HR) were recorded after infusion of noradrenaline (NA, 0.1 micromol l(-1)), glyceryl trinitrate (GTN, 1-100 micromol l(-1)), S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 1-10 micromol l(-1)) and N(omega)-nitro-L-arginine (L-NOARG, 0.1-1 mmol l(-1)). 3. Long-term hypertension induced myocardial hypertrophy and an abnormal response to NA. The relative heart weight (in mg kg(-1)) increased from 2.95 +/- 0.04 (WIS) to 6.67 +/- 0.34 (SHR15), while the increase in +dP/dt(max) induced by NA was absent in SHR15. Hearts of SHR10 showed an intermediate response. 4. Both SNAP and GTN significantly increased LVP, +dP/dt(max) and -dP/dt(max) in hearts of WIS and of SHR. In WIS but not in SHR10, SNAP also increased HR. In SHR10 the lowest concentration of SNAP (1 micromol l(-1)) showed no effect on contractility but a significantly diminished reduction of CPP suggesting inactivation of extracellularly released NO in the coronary circulation of SHR. 5. L-NOARG significantly reduced contractility in hearts of WIS and of SHR to a similar extent. At a concentration of 1 mmol l(-1) L-NOARG also reduced HR. 6. These results suggests that positive inotropic effects of exogenous and endogenous NO are not changed in hypertension induced myocardial hypertrophy.
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PMID:Positive inotropic effect of exogenous and endogenous NO in hypertrophic rat hearts. 938 95

5-Bromo-2'-deoxyuridine (BrdU) was administered intraperitoneally to Sprague-Dawley rats at doses of 50 mg/kg/d on Days 9 through 15 and at 100 mg/kg/d on Days 16 through 20 of gestation. Dams were allowed to deliver naturally. Male offspring were subjected to a variety of pre- and postweaning behavioral tests: surface righting, negative geotaxis, open field test, Biel maze test, wheel cage test, and shuttlebox avoidance test. After puberty, masculine sexual behavior was observed. Male offspring of dams treated with BrdU on Days 9 through 15 of gestation showed an accelerated negative geotaxis reflex and increased ambulation and rearing in open field, while those of dams treated on Days 16 through 20 of gestation showed normal activity. Offspring of dams treated on Days 9 through 15 of gestation showed a higher activity level in the wheel cage than offspring of dams treated on Days 16 through 20 of gestation. In the Biel maze, offspring of dams treated on Days 9 through 15 of gestation showed impaired learning and memory. In the shuttlebox avoidance response, offspring of dams treated on Days 9 through 15 of gestation moved significantly more than offspring of dams treated on Days 16 through 20 of gestation. Masculine sexual behavior was markedly reduced in male offspring of dams treated on Days 9 through 15 of gestation. However, no significant differences between groups in blood pressure nor heart rate were noted. We conclude that male offspring of dams treated with BrdU on Days 9 through 15 of gestation are hyperactive without hypertension and that these offspring show an impairment of masculine sexual behavior, i.e., hyposexuality.
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PMID:Behavior and reproductive function of rat male offspring treated prenatally with 5-bromo-2'-deoxyuridine. 976 46

Myocardial hypertrophy is characterized by abnormal intracellular Ca2+ handling and decreased contractile performance. Ca2+/calmodulin-dependent protein kinase II (CaMKII) phosphorylates numerous Ca2+ handling proteins and thus can regulate intracellular Ca2+ homeostasis directly. We therefore investigated whether differential expression of CaMKII isoforms occurs with cardiac hypertrophy which might promote an abnormal intracellular Ca2+ homeostasis. We further investigated the potential influence of angiotensin (Ang) II on CaMKII expression levels. Hearts from adult Spontaneously Hypertensive Rats (SHR) and hearts from two transgenic rat models with Ang II-dependent hypertension were studied. The expression of the cardiac CaMKII isoforms delta2, delta3, delta4 and delta9 was determined by RT-PCR and immunoblot methods. Rats transgenic for the mouse Ren-2 gene (mrTGR), SHR and controls were studied at the age of 6 months and rats transgenic for the human renin-angiotensin system (hrTGR) from postnatal day 1 to week 8. SHR and mrTGR had an increased heart/body weight ratio (26 and 25%) compared with controls (p < 0.05). SHR hearts showed significantly increased mRNA levels of delta4 and delta9 (p < 0.05) with no change for delta2 and delta3. mrTGR hearts had a significantly increased delta4 and a significantly decreased delta3 transcript level (p < 0.05) with no change for delta2 and delta9. hrTGR hearts developed severe hypertrophy (42%) after postnatal day 14. The neonatal delta2, delta3 and delta4 isoform expression levels were higher (30-100%) compared with SD controls. The levels decreased with increasing age and equalized to controls at week 8, except for delta4 which started to increase after week 4 (p < 0.05). CaMKIIdelta protein levels of all cardiac hypertrophy models were increased in sarcoplasmic reticulum preparations (50-120%) compared with controls (p < 0.05) while the cytosolic levels remained unchanged. Thus, CaMKIIdelta isoforms are differentially expressed in cardiac hypertrophy. The fetal delta4 isoform was constantly expressed. CaMKIIdelta adopts the fetal phenotype independent of the type of hypertrophic stimulus. The observed alterations of CaMKIIdelta isoform patterns may affect intracellular Ca2+ homeostasis and thus contribute to the abnormal contractile phenotype of cardiac hypertrophy.
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PMID:Expression of Ca2+/calmodulin-dependent protein kinase II delta-subunit isoforms in rats with hypertensive cardiac hypertrophy. 1145 85


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