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Biomedical subjects

M Nordlander

Publications and source records attributed to M Nordlander.

At least 37 records · Page 2Linked to original sources
PubMed1993

Coronary venous retroinfusion of felodipine reduces myocardial necrosis after coronary occlusion and reperfusion.

The effect of the vasoselective calcium antagonist felodipine on myocardial necrosis was studied in 14 anesthetized pigs subjected to 45-min occlusion of the left anterior descending coronary artery (LAD) followed by 24-h reperfusion. Felodipine (7 nmol/kg, n = 7), or the corresponding amount of vehicle diluted in 300 ml saline (n = 7) was infused in the great cardiac vein for 30 min beginning 5 min before onset of reperfusion. Regional myocardial function was measured as percentage of systolic segment shortening (%SS) by sonomicrometry. The recovery in ischemic myocardium was significantly already better among felodipine-treated animals after 30-min reperfusion (mean +/- SD = 9.1 +/- 6.1 vs. 0.1 +/- 3.2%, p < 0.05). The improved recovery in the felodipine group persisted throughout the observation period; %SS was 8.5 +/- 5.9% after 24-h reperfusion. No significant improvement was observed in the vehicle group after 24 h (%SS = 2.7 +/- 2.0%, p < 0.05). The area of the infarct was measured by triphenyl tetrazolium chloride staining. When expressed as percentage of the left ventricle, the infarct was smaller in the felodipine group (8.2 +/- 4.0%) than in the vehicle group (14.6 +/- 3.5%; p < 0.01). The corresponding values for infarct size expressed as percentage of the area at risk was 38.6 +/- 18.9% in the felodipine group and 69.8 +/- 6.7% in the vehicle group (p < 0.01). Peak plasma felodipine concentration was reached 30 min after onset of reperfusion (4.9 +/- 1.2 nM).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of felodipine on utero-placental blood flow in normotensive rabbits.

The utero-placental blood flow was investigated in anaesthetized normotensive pregnant rabbits after repeated administration of a high dose of the antihypertensive calcium antagonist felodipine and in untreated controls. By means of the microsphere technique blood flow was also determined in the lungs, skin, intestine, skeletal muscle and kidneys during chloralose anaesthesia. Felodipine reduced mean arterial blood pressure, which was associated with a marked reduction in vascular resistance in the skeletal muscle vascular bed, where blood flow was increased seven-fold. In contrast, blood flow to placentae and kidneys were reduced. The pronounced reduction in placental blood flow may limit foetal nutrition and hence explain reported foetal digital defects after administration of high doses of felodipine to pregnant normotensive rabbits.

Administration, Oral↗
PubMed1992

Trophic effects of hypophyseal hormones on resistance vessels and the heart in normotensive and renal hypertensive rats.

UNLABELLED: Arterial pressure is an important determinant of cardiovascular structure and relates positively to it. The purpose of this study was to determine whether pituitary hormones influence the relation of pressure and structure. Male Sprague-Dawley rats, aged 5 weeks, were studied in three groups: the first underwent hypophysectomy; the second was hypophysectomized but received replacement therapy with growth hormone and thyroxine; the third served as controls. Four days later half of each group underwent unilateral renal artery clipping, the other half serving as normotensive controls. For 5 weeks estimates were made of systolic blood pressure, heart rate, body weight and plasma renin activity. Rats were then killed; left ventricular, kidney and adrenal weights were determined and, using hindquarter perfusion, estimates were made of resistance at maximal dilatation (reflecting inner radius), and of maximal pressor response (reflecting wall thickness). RESULTS: (1) Hypophysectomy in non-clipped rats reduced growth rate, systolic blood pressure and heart rate while plasma renin activity rose. As related to pressure and to body weight, resistance at maximal dilatation, maximal pressor response, left ventricular weight remained at the juvenile values of a 5-week-old rat. Hormone replacement restored values to those of control rats aged 11 weeks. (2) Clipping in the control group rats increased systolic blood pressure more than in hypophysectomized and growth hormone and thyroxine receiving hypophysectomized groups even though plasma renin activity remained higher in hypophysectomized than in control rats. Plasma renin activity was highest in hypophysectomized rats with highest pressure. (3) Systolic blood pressure related positively to left ventricle weight, resistance at maximal dilatation, maximal pressor response and calculated wall thickness to inner radius ratios in all groups. However, these regressions were all, like renal structural adaptation, considerably depressed in the hypophysectomized group. Hormone replacement restored the relation of structure and pressure towards that of control group rats. Thus, growth hormone and thyroxine influence maturation of the normal cardiovascular system and greatly enhance its structural upward resetting in hypertension.

Animals↗
PubMed1992

Functional and stereologic estimations of myocardial capillary exchange capacity in treated and untreated spontaneously hypertensive rats.

Myocardial capillary exchange capacity was investigated by stereologic and functional techniques in parallel during pressure-overload cardiac hypertrophy and after long-term antihypertensive therapy with the vasodilator felodipine. In 26-week-old female spontaneously hypertensive rats (SHR) blood pressure increased by 25% and left ventricular weight (LVW/BW) increased by 18% compared to Wistar-Kyoto rats (WKY). Myocardial capillary surface and volume densities normalized for organ weight were similar in both ventricles for both strains. Moreover, capillary surface density was higher sub-epicardially (EPI) than in the subendocardium (ENDO) in the left ventricle of SHR. Thirteen weeks of felodipine-therapy (SHR-Felo) normalized blood pressure without affecting LVW/BW although a transition from concentric to eccentric hypertrophy is known to occur. Myocardial capillary surface and volume densities and the left ventricular ENDO-EPI-gradient in surface density were similar to untreated SHR. However, felodipine-treatment increased right ventricular weight and capillary volume density. Functional capillary exchange was estimated in terms of permeability surface area products (PS) for Cr-EDTA and vitamin B12 and normalized for organ weight. PSCr-EDTA, PSB12 and the ratio PSCr-EDTA/PSB12 (an index of capillary permeability) were similar in SHR and WKY. Furthermore, the relation between functional and stereological indices of exchange capacity was investigated in a multiple linear regression analysis. However, no significant correlation between PS and neither capillary surface nor volume density was found. In conclusion, myocardial capillary exchange capacity was well adapted to the pressure overload cardiac hypertrophy present in female SHR. Despite induction of right ventricular hypertrophy, felodipine-treatment did not affect capillary exchange capacity. Furthermore, when functional and stereologic estimates were performed in parallel, the importance of dynamic factors for myocardial capillary exchange capacity (e.g. heterogeneity) was illustrated.

Animals↗
PubMed1992

Influence of early antihypertensive treatment on vascular and cardiac design in SHR with and without renal hypertension.

The present study was designed to explore to what extent pressure reduction by antihypertensive therapy and pressure elevation by renal hypertension are able to affect structural vascular and cardiac changes in young spontaneously hypertensive rats (SHR). Pressure elevation in SHR was induced by means of superimposing 2 kidney, 1 clip renal hypertension (2K1C). Pressure reduction was achieved by means of the vasoselective calcium antagonist felodipine from 6 to 13 weeks of age in both clipped and unclipped SHR. Vascular structure of the skeletal muscle was assessed hemodynamically by perfusing a hindlimb preparation and left ventricular dimensions were calculated from pressure-volume relationships of isolated hearts arrested in diastole. Induction of renal hypertension in SHR resulted, besides augmentation of arterial pressure in a marked concentric left ventricular hypertrophy, i.e. elevations of wall thickness to internal radius ratio. Likewise, in renal hypertensive SHR, a structural adaptation of the skeletal muscle vascular bed occurred, reflected as elevations of minimal vascular resistance and maximal generated perfusion pressure. Antihypertensive treatment for 8 weeks with felodipine reduced and also prevented mean arterial pressure from increasing further in SHR, and in SHR with superimposed renal hypertension by approximately 15% (p < 0.001 for both). In renal hypertensive SHR, felodipine partly prevented the development of exaggerated structural changes, both in the heart and in the skeletal muscle vascular bed, as reflected by reduced wall thickness to internal radius ratio and reduced minimal vascular resistance by 22% and maximal pressure response by 10% respectively (p < 0.01 for both parameters).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of chronic felodipine treatment on renal function and morphology in SHR.

To investigate if blood pressure reduction per se may prevent progressive renal disease in aging spontaneously hypertensive rats (SHR), 15-month-old SHR were treated with the calcium antagonist felodipine, with the beta-blocker metoprolol or with the combination for six months. The combined regimen caused the greatest blood pressure reduction over time, metoprolol caused the least, while felodipine had an intermediate effect. At the end of treatment, urinary protein excretion and endogenous creatinine clearance were determined in rats kept in individual metabolic cages. At autopsy, the kidneys were histologically examined and indices of chronic progressive nephrosis and glomerular sclerosis were determined. A positive correlation was found between urinary protein excretion and glomerular sclerosis. Glomerular sclerosis was low in the groups of rats with high endogenous creatinine clearance. In both groups treated with felodipine, glomerular sclerosis and urinary protein excretion were significantly reduced compared to untreated controls. These results illustrate that the calcium antagonist felodipine attenuates proteinuria and glomerular sclerosis in aging SHR. The blood pressure reduction may be of major importance in this respect, although a direct action on the sclerotic process within the glomeruli may also contribute.

Animals↗
PubMed1992

Renal effects of felodipine--a review.

Felodipine is a dihydropyridine calcium antagonist which lowers total peripheral resistance and blood pressure in doses which have no effect on cardiac conduction and contractility. It increases the urinary excretion of sodium and water due to decreased renal tubular reabsorption from the glomerular ultrafiltrate. This is observed at low doses which do not affect blood pressure, renal blood flow (RBF) or glomerular filtration rate (GFR). Felodipine decreases total renal vascular resistance and causes a transient increase in RBF in patients with normal RBF. In patients with low pretreatment values, RBF is increased during chronic treatment. Felodipine does not affect normal GFR. Thus filtration fraction may decrease. In patients with severe hypertension and reduced GFR, felodipine treatment results in good blood pressure control and increased GFR. In animal models of progressive renal disease due to hyperfiltration, felodipine has no negative effect on GFR, glomerulosclerosis or survival although proteinuria may increase. In salt-sensitive rats given high salt diet, resulting in hypertension, hypoperfused kidneys and progressive renal damage, felodipine treatment results in reduced blood pressure, increased RBF and GFR, and reduced proteinuria and glomerulosclerosis. In patients with previously refractory hypertension and progressive impairment of renal function, felodipine treatment results in good blood pressure control and a reduced rate of progression. In animals, felodipine limits the extent of renal damage after ischemia and reperfusion.

Animals↗
PubMed1991

Acute haemodynamic effects of felodipine, verapamil and hydralazine in the anaesthetized dog.

Felodipine, a potent dihydropyridine calcium antagonist with a pronounced vascular selectivity, was given intravenously (0.006-0.025 mumol kg-1) to anaesthetized, open-chest dogs with denervated hearts. The result was a dose-dependent decrease in mean arterial pressure (MAP) and total peripheral resistance (TPR), while heart rate (HR), stroke volume (SV) and left ventricular end-diastolic pressure remained relatively unchanged. Cardiac tension work (TTI) and oxygen consumption (MVO2) were reduced, probably due to the decrease in afterload. The relative reduction of the coronary vascular resistance (CVR) was greater than that of TPR. The hypotensive effect of verapamil (0.05-0.20 mumol kg-1) was small and MAP decreased mainly via a decrease in HR and SV. Higher doses of verapamil which induced vasodilatation could not be given without the development of complete atrio-ventricular dissociation. Hydralazine (11-45 mumol kg-1) decreased TPR and CVR in parallel but the decrease in MAP was partly counteracted by a powerful increase in HR, SV and cardiac inotropy which was associated with elevated catecholamine levels in plasma. When MAP and HR were maintained constant by means of aortic balloon inflation and atrial pacing, felodipine markedly increased coronary blood flow and coronary sinus oxygen saturation while SV, TTI, inotropy and MVO2 remained relatively unchanged. It is concluded that felodipine markedly dilates peripheral resistance vessels, and in particular those in the coronary vascular bed, without any cardiodepressant effects.

Animals↗
PubMed1991

Low-dose felodipine treatment attenuates endothelial dysfunction in rabbits fed an atherogenic diet.

Loss of endothelium-dependent relaxation is an early step in atherogenesis. To test the effect of low-dose felodipine on the progression of this dysfunction, male New Zealand white rabbits were rendered hypercholesterolemic with a diet containing 0.25% cholesterol and 3% coconut oil. After a 1-month induction period on this diet, during which the rabbits were identified as low or normal responders to cholesterol, 0.46 mg/kg of felodipine (FELO) or placebo (CON) were given by gavage once daily for a further 3 months. This regimen established FELO plasma levels (14.2 +/- 1.3 nM, week 9) corresponding to therapeutic concentrations in humans and an average 13-fold increase in plasma cholesterol from below 1 mM. At the end of the treatment period, relaxation of norepinephrine (1 x 10(-8) M)-precontracted proximal thoracic aorta strips to acetylcholine (ACh: 1 x 10(-8)-1 x 10(-5) M) was determined. Cholesterol exposure was calculated as the area under the curve for serum cholesterol x time [AUC (mM x day 1)]. Despite equal cholesterol load [FELO (n = 17): 1,856 +/- 182 mM x day) and CON (n = 22): 1,851 +/- 167 mM x day], maximal relaxation to 1 x 10(-7) M ACh was well preserved in strips from FELO-treated rabbits (29.5 +/- 5.7%) but suppressed in strips from untreated rabbits (11.0 +/- 2.9%). For comparison, relaxation in strips from standard diet controls was 49.8 +/- 2.9% (n = 15). Moreover, there was a significant inverse correlation (r = -0.74) between percentage ACh relaxation and cholesterol exposure in FELO-treated rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1990

Hemodynamic effects of calcium antagonists with high or low vascular selectivity.

Infusion of felodipine and verapamil in increasing doses to anesthetized spontaneously hypertensive rats induced a progressive fall in arterial blood pressure (BP). To estimate the cardiac action of the different drugs, we also measured changes in cardiac output (CO) and velocity of flow (dF/dT) by a Doppler flow probe placed on the ascending aorta. Infusion of verapamil induced a parallel decrease in mean arterial BP, CO, and cardiac inotropy (as estimated by max. dF/dT). In contrast, upon felodipine administration, the decrease in arterial BP was accompanied by an initial small rise in dF/dT. A decrease in dF/dT was observed only after high doses of felodipine, which caused pronounced levels of hypotension.

Animals↗
PubMed1989

Autonomic control of the diurnal variation in arterial blood pressure and heart rate in spontaneously hypertensive and Wistar-Kyoto rats.

The relative influences of sympathetic and parasympathetic neural modulation on mean arterial pressure (MAP) and heart rate (HR), and their respective variabilities, were studied in young spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). An on-line computerized system was used for continuous intra-arterial measurements of MAP and HR in unrestrained rats. In addition, the autonomic nervous control of MAP and HR was studied in ageing SHR and WKY. Both WKY and SHR showed diurnal rhythms with regard to MAP and HR. The MAP variability was higher in SHR than in WKY during both daytime (inactive) and night-time (active), and did not change in response to either beta 1-adrenoceptor- or cholinergic blockade. Structural vascular changes, with a resultant increase in reactivity, may explain the elevated MAP variability in SHR. HR variability was clearly reduced in SHR; this was not influenced by vagal blockade, whereas HR variability was significantly reduced in WKY. This pattern is suggested to be due to a reduced tonic vagal discharge in SHR, as part of a persistent, mild defence reaction. The initial reduction in vagal activity will in turn eliminate vagally mediated tachycardias. Furthermore, administration beta 1-blockade to SHR of different ages caused a greater fall in MAP and HR than in WKY, indicating an increased dependence upon the sympathetic nervous system in SHR with age.

Animals↗
PubMed1989

Functional and biochemical analyses of isolated rat hearts in renal and reversed renal hypertension.

The present study evaluates cardiac function, plasma renin activity (PRA) and left ventricular (LV) myosin isoenzymes in untreated two-kidney, one-clip Goldblatt hypertensive rats (2KIC) and in 2KIC treated with felodipine and metoprolol. Normotensive rats (NCR) and another group of 2KIC, in which the renal artery constriction was removed (UC-2KIC), were also investigated. Cardiac performance was assessed by means of a working heart perfusion device, allowing also for measurements of myocardial oxygen consumption. Following antihypertensive therapy and unclipping, blood pressure became close to normotensive levels. PRA remained equally elevated in treated and untreated 2KIC, but became practically normalized after unclipping. Relative LV weight in 2KIC increased 74% above that in NCR but in treated 2KIC increased by only 20%. In UC-2KIC LV hypertrophy became reversed, LV weight/body being about the same as in treated 2KIC. In treated 2KIC, coronary resistance at maximal dilatation was significantly reduced, implying prevention of hypertensive, structural coronary vascular changes, and optimal LV function was improved markedly in the lower range of perfusion pressures compared with untreated 2KIC. When, however, the hearts were challenged at a high pumping resistance (perfusion pressure), LV function was similar in untreated and treated 2KIC. Myocardial oxygen consumption for given levels of stroke work was significantly lower in treated than in untreated 2KIC. The myosin isoenzyme pattern in the LV of 2KIC was shifted, with significantly higher amounts of VM-3 than in NCR. This shift was normalized by antihypertensive therapy or by unclipping. In conclusion, antihypertensive therapy with felodipine and metoprolol prevents the development of coronary vascular and left ventricular hypertrophy in 2KIC. This may contribute to enhance cardiac performance at low aortic pressure. The lack of improvement in optimal cardiac performance (at high aortic pressure) implies that the hypertensive state per se, rather than extent of pressure elevation, cardiac hypertrophy, or changes of LV isoenzymes, determines the reduced cardiac function in renal hypertensive rats (Friberg & Nordborg 1986).

Animals↗
PubMed1988

Sympathetic and parasympathetic influence on blood pressure and heart rate variability in Wistar-Kyoto and spontaneously hypertensive rats.

The relative influence of sympathetic and parasympathetic nervous control of heart rate and heart rate variability, of mean arterial pressure (MAP) and MAP variability was investigated in young spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). An on-line computerized system was used for continuous intra-arterial measurements of MAP and heart rate every 2.5 min in freely moving rats with indwelling arterial catheters. Variability was expressed as the standard deviation in each rat. Heart rate and MAP showed clear diurnal rhythms, both in WKY and SHR. Blood pressure variability was clearly higher in SHR than in WKY, both during dark active hours and during light hours of relative sleep, and it did not change in response to either beta-adrenoceptor or vagal blockade. Structural vascular changes with the consequent increase in vascular reactivity may be one explanation for the elevated blood pressure variability in SHR. Heart rate variability was clearly reduced in SHR compared with WKY. This may be due to a reduced tonic vagal discharge in SHR, whereby a vagally mediated tachycardia is eliminated. The vagal withdrawal is part of the defence reaction, which is more easily elicited in SHR than in WKY.

Animals↗
PubMed1988

Mechanisms behind myocardial depression in rat renal hypertension.

Cardiac function in rat renal hypertension has been shown repeatedly to be depressed. The reason for this impairment has not been fully understood, although cardiac hypertrophy and increased collagen content have been claimed as possible causes. To further unravel the mechanisms underlying the deterioration of left ventricular function in rat renal hypertension, we investigated cardiac function, myocardial morphology, myosin iso-enzymes, plasma renin activity and levels of myocardial high-energy compounds in hearts from rats exposed to renal and reversed renal hypertension. Maximal cardiac function was unaltered in hearts exposed to antihypertensive therapy from the time of renal artery clipping compared with untreated hypertensive rats. The observed alterations of iso-enzyme pattern, plasma renin activity levels and myocardial morphology among the groups showed to be of less importance with respect to cardiac performance. Together with previous results from our laboratory, the present findings suggest that some negative inotropic agent of renal or non-renal origin is released during two-kidney, one clip renal hypertension, which counteracts the enhanced left ventricular performance induced by cardiac hypertrophy.

Adenine Nucleotides↗
PubMed1988

The importance of hypophyseal hormones for structural cardiovascular adaptation in hypertension.

The effect of renal artery clipping was tested in three groups of male Sprague-Dawley rats: (1) 30 control animals, (2) 30 hypophysectomized animals, and (3) 30 hypophysectomized animals treated with growth hormone and thyroxine. Fifteen rats in each group were clipped and 15 acted as controls. In the first group clipping raised arterial pressure and plasma renin activity. Thirty-five days after clipping, pair-perfused hindquarter preparations at maximal dilation and maximal pressor response were both increased, reflecting, respectively, decreased lumen diameters and increased media thickness in the resistance vessels. Clipping also increased left ventricular weight. Hypophysectomy eliminated the weight gain, and the maximal pressor response and maximal dilation were lower than in the control and treated groups. Hypophysectomy also considerably reduced the rise in blood pressure on clipping and, even more so, the associated structural cardiovascular changes. Replacement therapy with growth hormone and thyroxine almost restored the weight gain and also the structural responses of the heart and vessels to clipping. We conclude that pituitary hormones play an important, probably permissive, part in the development of normal vessel structure and in the adaptation of cardiovascular structure to chronic hypertension.

Animals↗
PubMed1988

Effects of voluntary physical exercise on cardiac function and energetics in spontaneously hypertensive rats.

The influence of voluntary physical exercise in running wheels on myocardial function, cardiac oxygen utilization and cardiovascular response to emotional stress was analysed in the spontaneously hypertensive rat. After 6 weeks of exercise, a significant increase in resting cardiac output was found, which was due to an elevation of stroke volume. However, voluntary training for 12 weeks had no effect on resting blood pressure or on the blood-pressure response to mental stress. Cardiac function was also examined in vitro. At a low aortic diastolic pressure, it was markedly augmented in trained spontaneously hypertensive rats. At high aortic diastolic pressure, maximal cardiac function was similar in the two groups. Myocardial oxygen consumption (mumol min-1 g-1) for a given level of external work was reduced in trained, compared with non-exercised control spontaneously hypertensive rats. Chronic physical exercise thus greatly improved myocardial function at a subnormal perfusion pressure, suggesting better nutritional supply to the myocardium, probably created by an increased capillary surface area.

Animals↗