Protein kinase C (PKC) is activated by alpha-adrenergic stimulation. Molecular analysis showed that PKC consists of a family of at least 12 isozymes. Studies of their distribution in the heart showed conflicting results. The first goal of our study was thus to characterize cardiac PKC in normal rabbits. PKC plays an important role in gene expression, cell growth, and differentiation and is involved in the hypertrophy phase of cardiac overload, but since its expression has never been evaluated in heart failure, the second goal of our study was to evaluate PKC activity and isoform expression in rabbits with heart failure induced by a double hemodynamic overload (aortic insufficiency followed by an aortic stenosis). In the first part of the study, PKC isoform expression analyzed in normal rabbits by immunoblotting showed that isoforms alpha, beta, epsilon, and zeta were expressed along with PKC gamma, which had never been detected in the heart. PKC gamma expression was also identified by polymerase chain reaction, and immunofluorescence techniques showed a localization on intercalated disks associated with the membrane localization observed with the other isoforms. In the second part of the study, PKC activity, content, and isoform expression showed a decrease of 37% in the failing group. PKC immunodetection with a monoclonal antibody (Mab 1.9) recognizing the catalytic domain of all PKC isoforms revealed a 20% decrease in the failing ventricles compared with normal left ventricles. Expressed PKC isoforms quantified by Western blot showed, in the failing heart group compared with the control group, a decrease of 27%, 32%, 16%, and 9% of PKC alpha, PKC beta 1, PKC gamma, and PKC epsilon, respectively, whereas PKC zeta was not significantly modified. These results show that, in heart failure, PKC activity and expression of Ca(2+)-dependent PKC isoforms are decreased. This may lead to alterations of PKC-induced phosphorylations.
Hyperlipidaemia, atherosclerosis and related diseases are becoming a major health problem in developing countries. Ocimum basilicum is one of the medicinal plants widely used in Morocco to reduce plasma cholesterol and to reduce the risk of atherosclerosis-related diseases. However, mechanisms underlying the reported hypolipidaemic effect of this plant have not been investigated. This study evaluates the lipid lowering effect of aqueous Ocimum basilicum extract in Triton WR-1339-induced hyperlipidaemic rats. Hyperlipidaemia was developed in animals by intraperitoneal injection of Triton (200 mg/kg). After injection of Triton the animals were divided into three treatment groups: hyperlipidaemic, hyperlipidaemic plus herb extract and hyperlipidaemic plus fenofibrate treated rats. At 7 h after the Triton injection, levels of plasma cholesterol, triglycerides and LDL-cholesterol in rats treated also with the Ocimum basilicum extract (0.5 g/100 g body weight) were, respectively, 50%, 83% and 79% lower than Triton-treated rats and HDL-cholesterol was 129% higher than in rats given Triton alone. At 24 h following Ocimum basilicum administration, total cholesterol, triglycerides and LDL-cholesterol levels decreased by 56%, 63% and 68%, respectively, in comparison with the Triton treated group and HDL-cholesterol was not increased significantly. The hypolipidaemic effect exerted by Ocimum basilicum extract was markedly stronger than the effect induced by fenofibrate treatments. Further it was demonstrated that Ocimum basilicum aqueous extract displayed a very high antioxidant power. These results indicate that Ocimum basilicum extract may contain hypolipidaemic and antioxidant substances and its use as a therapeutic tool in hyperlipidaemic subjects may be of benefit and encourage further investigation in this field.
Few models of heart failure (HF) are available for physiological and pharmacological studies. We report here a model of pressure plus volume overload induced in rabbits in which left ventricular (LV) function was studied in the conscious state after instrumentation of the animals with LV pressure catheter and ultrasonic crystals measuring LV diameter. Beta-Adrenoceptors were studied on crude membranes obtained from control (C) and HF rabbits using [3H]CGP 12177. LV weights and end-diastolic diameters were significantly increased in the HF group compared with the C group (by 79 and 38%, respectively). The percentage of diameter systolic shortening was decreased, in the control state, in rabbits with HF (15.3 +/- 1.6%) as compared with C rabbits (29.6 +/- 2.5%) and remained lower in the HF group when end-systolic pressures were matched. Chronotropic response to isoproterenol injection was significantly decreased in rabbits with HF compared with that of C rabbits. Beta-Adrenergic receptor density was decreased in rabbits with HF (39.3 +/- 3.7 fmol/mg) compared with C rabbits (56.7 +/- 4.2 fmol/mg) without affinity changes. This model of chronic HF thus produces a marked hypertrophy with ventricular dilatation and a depression of LV function within 2 mo, factors that are associated with a reduced cardiac responsiveness to catecholamines and a decreased ventricular beta-adrenergic receptor density.
The major objectives of this work are to estimate the hypertension (HT) frequency in the east of Morocco and to study the relationship between HT, type 2 diabetes and obesity. Our sample is composed of 1628 adults aged 40 years and older, recruited voluntarily by using the convenience sampling method through 26 screening campaigns in urban and rural areas of the east of Morocco. We enumerated 516 hypertensive people (31.7%), without significant difference between women (32.5%) and men (30.2%). The known hypertensive people represent 10.1% of the whole sample. The frequency of HT, increases with age and it is more marked in rural (39.9%) than in urban areas (29%) (p < 0.001). It is significantly very high in diabetic subjects (69.9%) than among the non-diabetic ones (27.4%) (p < 0.001). The odd ratio (OR) of the diabetics to HT is 6.16 (IC95% [4.33-8.74]). Among the obese persons, HT is present at (40.8%) vs. (30.2%) among the subjects of normal weight (p < 0.05). The OR of the obese to HT is 1.6 (IC95% [1.26 - 2.04]). In conclusion, our results show a high frequency of HT in the east of Morocco; it affects nearly one third of the adult population aged 40 years and older. The relations between type 2 diabetes and obesity have also been identified and estimated.
Force-frequency relations were studied in an isolated-perfused rabbit heart model. Heart failure was induced by a double volume plus pressure overload. Studies were performed at the early stage of heart failure when basal ventricular function was not decreased. The normal positive staircase induced by pacing in control hearts (CH) was replaced by a negative staircase in failing hearts (FH) with an increase in end-diastolic pressure for increased heart rates in FH. Postpacing potentiation and postextrasystolic potentiation (PESP) were significantly reduced in FH as compared with CH. Ventricular function decreased by 60% in both CH and FH under ryanodine with similar dose-response curves. Postpacing and PESP disappeared under ryanodine in CH and in FH with a reversal of the negative staircase in FH. The abnormal force-frequency relations observed in heart failure are thus attributed to sarcoplasmic reticulum dysfunction. Basal ventricular function during spontaneous heart rate may be normal in the early stage of heart failure, but sarcoplasmic reticulum dysfunction produces abnormalities in ventricular function when heart rate is abruptly modified, particularly during tachycardia.
Heart failure is usually characterized by a relative insensitivity to atrial natriuretic factor (ANF). Downregulation of ANF receptors has been reported but remains controversial. Renal response to ANF infusion, glomerular ANF receptors, and guanosine 3',5'-cyclic monophosphate (cGMP) production have been studied in rabbits with congestive heart failure (CHF) after traumatic aortic regurgitation and abdominal aortic stenosis. Diuresis and natriuresis induced by ANF infusions were significantly decreased in CHF animals. Plasma cGMP was higher in CHF rabbits before ANF administration than in controls (37.6 +/- 7.2 vs. 17.1 +/- 3.9 pmol/ml, P < 0.02) and increased to a same level after ANF in both groups (48.8 +/- 4.2 vs. 52.5 +/- 2.8 pmol/ml, NS). No difference was found in glomerular ANF receptor density (436 +/- 54 vs. 425 +/- 57 fmol/mg protein, NS) nor in affinity between the two groups (dissociation constant; 240 +/- 24 vs. 347 +/- 49 pM, NS). Moreover, in vitro glomerular cGMP production in response to exogenous ANF was preserved. In conclusion, despite a blunted renal response to ANF in vivo, glomerular ANF receptors were unchanged in this model, and no defect in cGMP production in response to ANF was found. This suggests the existence of an intracellular defect beyond the second messenger.
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