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H A Struyker-Boudier

Publications and source records attributed to H A Struyker-Boudier.

At least 19 recordsLinked to original sources
PubMed1997

Cardiac function in a rat model of chronic aortic stiffness.

Cardiac function was investigated in conscious normotensive rats in which increased aortic stiffness was produced as a result of vascular calcium overload after treatment with vitamin D3 plus nicotine (VDN rats, n = 16; controls, n = 17). Baseline stroke volume, cardiac output, and cardiac response to a venous volume overload were unchanged after 1 mo of exposure to increased aortic stiffness, as were baseline venous return and total vascular capacitance. The latter was estimated from the change in mean circulatory filling pressure after modification of circulatory volume. Cardiovascular reflexes were modified in VDN rats. Bradycardia evoked by an increase in arterial PCO2 (PaCO2) or hypotensive hemorrhage was more pronounced. The PaCO2-induced bradycardia was accompanied by a fall in cardiac output in VDN rats but not in controls. In VDN rats, the attenuation of sympathetic reflexes may explain the slower recovery of blood pressure after hypotensive hemorrhage. In conclusion, a chronic increase in aortic stiffness does not compromise cardiac performance, but cardiovascular reflexes are impaired in VDN rats. Whether this is because of the increase in aortic stiffness or the effect of VDN treatment on the baroreceptors or other components of the reflex arc remains to be elucidated.

Animals↗
PubMed1995

Mechanical and contractile properties of in situ localized mesenteric arteries in normotensive and spontaneously hypertensive rats.

An in situ model was developed for studying mechanical properties of mesenteric arteries in rats. A branch of the mesenteric artery was exposed and dissected in normotensive (WKY) and spontaneously hypertensive rats (SHR). A catheter was introduced into the larger branch of the mesenteric artery and connected to a pressure chamber. The artery was submitted to transmural pressures ranging from 0 to 200 mmHg per steps of 25 mmHg and observed using a microscope-video-camera system. The diameter-pressure relations were established under basal conditions, under contraction (phenylephrine 10(-6) M), and after abolition of the smooth muscle tone by potassium cyanide (KCN, 0.1 mg/mL). The arterial segment was then fixed (glutaraldehyde 2.5%), and the wall cross-sectional areas were measured in transverse sections. Compliances, distensibility, wall tensions, and wall stresses were calculated from diameter, pressure, and media thickness values under three conditions. Active tension and active stress were defined as differences in wall stresses and wall tensions calculated under passive and active conditions. Comparison of WKY and SHR when arteries were studied at the respective operating pressure indicates (1) thicker and stiffer mesenteric arteries in SHRs than in WKY rats, (2) similar wall stresses in mesenteric arteries from WKY and SHRs despite larger wall tensions in the hypertensive group, and (3) larger contractility to phenylephrine in SHRs than in WKY mesenteric arteries.

Animals↗
PubMed1993

Renal selective N-acetyl-L-gamma-glutamyl prodrugs: studies on the selectivity of some model prodrugs.

1. In this study, a number of structurally different N-acetyl-L-gamma-glutamyl prodrugs were investigated with respect to selective uptake by the kidney in male Wistar rats. 2. All prodrugs were tested in vitro in rat kidney slices and kidney homogenate to study their uptake and conversion. It was found that the prodrugs of para-nitroaniline (agPNA), aminophenyl acetic acid (agAFA), sulphamethoxazole (agSM), sulphadimethoxine (agSDM), propranolol (agPP) and metoprolol (agMP) were accumulated by a probenecid-sensitive carrier. The prodrug of 4'-aminoantipyrine (agAAP) was not accumulated by a probenecid- or buthionine sulphoximine-sensitive carrier. Unlike all other prodrugs, agAAP and agMP were not, or only a very limited extent converted to the parent compound in vitro. 3. agPNA, agAFA and agPP were also investigated in vivo. The tissue distribution of the prodrugs and the parent drugs was established, as was their urinary excretion and pharmacokinetic behaviour. agPNA and agAFA showed selective uptake by the kidney, in contrast to agPP which accumulated in the liver. The distribution of the parent compounds following prodrug administration was as follows: agPNA was found in kidney and plasma: agAFA in kidney only; agPP in liver only. 4. The factors which determine the selectivity of N-acetyl-L-gamma-glutamyl prodrugs are discussed. The main factors are: the transport into the kidney, the conversion rate, the residence time of the prodrug in the kidney and the presence or absence of competition for uptake and conversation by other tissues, e.g. the liver. It is concluded that this prodrug approach offers the possibility of delivering drugs selectively to the kidney, but also that it is not universally applicable.

Ampyrone↗
PubMed1993

Time-dependent efficacy of antihypertensive agents in spontaneously hypertensive rats.

The efficacy of antihypertensive agents was compared when given at different time points in the circadian rhythm. Spontaneously hypertensive rats (SHRs) were kept on a 12/12-h cycle with lights on/off at 07:00/19:00 h. A computerized system was used to measure intraarterial blood pressure and heart rate continuously. Agents or vehicle were intravenously injected at two time points. One at the beginning of the sleeping period, at which low efficacy was expected (T = 10), and one at T = 16, which is 3 h before the circadian peaks in blood pressure (BP) and heart rate (HR), aimed at reducing the rise in BP and HR at awakening. The hypotensive effect of propranolol, metoprolol, labetalol, prazosin, clonidine, and rilmenidine was greater when injected at T = 16 than at T = 10 (p < 0.05 for propranolol, metoprolol, and rilmenidine). In contrast, the renal vasodilators captopril and tertatolol were more potent after injection at T = 10. Felodipine was equally effective at both time points. Thus, the effects of antihypertensive agents are related to the phase of the circadian rhythm. The data on the sympatholytic agents in general and beta-blockers and centrally acting agents in particular support antihypertensive regimens with timed administrations.

Animals↗
PubMed1992

Compliance and reactivity of the peripheral venous system in chronic intermittent hemodialysis.

A reduced venous compliance and/or inadequate venoconstriction could impair hemodynamics during hemodialysis. Therefore, compliance and reactivity of the peripheral venous system were assessed in hemodialysis patients and controls using strain gauge plethysmography. Reactivity of the venous system towards an efferent sympathetic stimulus was assessed using a cold pressor test. Results showed that venous compliance was reduced in hypertensive hemodialysis patients compared to normotensive dialysis patients (P = 0.013) and normotensive controls (P = 0.004). After one dosage with a directly acting venodilator (nitroglycerin 5 mg s.l.) and 3 days of treatment with an alpha 1-sympathicolytic agent (Doxazosin 2 mg), venous compliance remained unaltered in hypertensive dialysis patients. During the cold pressor test, the blood pressure response, rise in noradrenaline levels and decline in venous compliance were normal in hemodialysis patients. However, their response to the Valsalva manoeuver was significantly impaired (P = 0.011) compared to healthy controls. We conclude that hypertension, not renal failure, causes the reduction of peripheral venous compliance in hemodialysis patients, for which structural factors might be responsible. Despite the existence of autonomous neuropathy, the reaction of the peripheral venous system towards an efferent sympathetic stimulus is intact in hemodialysis patients.

Adrenergic alpha-Antagonists↗
PubMed1992

Acute renal vascular response to ACE inhibition in two rat strains with different susceptibility to the development of glomerulosclerosis.

Normotensive male Wistar rats are susceptible to the development of glomerulosclerosis, a process which can be accelerated by partial renal ablation, while normotensive male Wistar Kyoto (WKy) rats are resistant to glomerulosclerosis. Long-term treatment with angiotensin-I-converting enzyme inhibitors prevents the development of glomerulosclerosis. We studied the acute renal vascular response to bolus injections of captopril (1, 3, and 10 mg/kg). Mean arterial blood pressure (MAP) was significantly less in Wistar rats compared to WKy and not influenced by unilateral nephrectomy. Renal vascular resistance (RVR) and the filtration fraction (FF) were significantly greater in sham and unilateral nephrectomy Wistar rats as compared to WKy. Captopril significantly reduced the RVR in all four groups, but at comparable doses, RVR remained greater in the Wistar sham and Wistar rats following unilateral nephrectomy compared to sham and uninephrectomized WKy respectively. Captopril reduced FF in Wistar rats only. These data indicate an enhanced level of activity of the renal renin-angiotensin system in glomerulosclerosis-susceptible Wistar rats compared to glomerulosclerosis-resistant WKy rats, suggesting that vascular reactivity involving the renin-angiotensin system is an important determinant of the genetically determined differences in susceptibility to glomerulosclerosis in these two rats strains. The strain-dependent difference in RVR at the highest dose of captopril indicates that additional, possibly structural features may play a role in the difference in susceptibility to glomerulosclerosis.

Animals↗
PubMed1991

Microvascular actions of calcium channel antagonists.

The microvascular actions of three calcium channel antagonists were studied in intact spontaneously hypertensive rats (SHR) provided with a dorsal striated muscle microcirculatory chamber. Verapamil and the dihydropyridine derivatives nifedipine and felodipine reduced mean arterial blood pressure (MAP) in a dose-dependent manner. They dilated arterioles of different sizes, with the most pronounced effect being on the smallest precapillary arterioles. Venular diameters were not affected by the calcium antagonists. Approximately 60% of the small arterioles showed a rhythmic pattern of vasodilatation and constriction. This pattern of spontaneous vasomotion was completely blocked by the calcium channel antagonists, especially those of the dihydropyridine type. It is concluded that (a) small precapillary arterioles play an important role in the vasodilator action of calcium channel antagonists, and (b) arteriolar vasomotion depends on vascular smooth muscle cell calcium influx.

Animals↗
PubMed1991

Delayed but not immediate captopril therapy improves cardiac function in conscious rats, following myocardial infarction.

After myocardial infarction, the renin-angiotensin system is found to be activated. While this response may be beneficial in acute failure, it could be detrimental in chronic stages. Therefore effects of captopril therapy were investigated during early and later phases after myocardial infarction in conscious rats, chronically instrumented for hemodynamic measurements. Hemodynamics were measured at baseline and after stimulating the heart by a volume load (cardiac function curve). Myocardial infarction decreased baseline cardiac output and impaired cardiac function, without effects on baseline mean arterial pressure, central venous pressure and heart rate. Captopril given 3 to 5 weeks after infarction improved cardiac function in a dose-dependent manner by increasing stroke volume, whereas stroke work was not affected. In contrast, captopril given from 1 to 21 days after infarction did not lead to improved cardiac function; instead, tachycardia together with a decreased stroke volume suggested deterioration, rather than improvement, of cardiac function. These data indicate that captopril therapy in chronically infarcted conscious rats improved cardiac function when treatment was started after completion of the healing process, but that early treatment not only failed to improve ventricular function, but may have a deleterious effect of the heart.

Animals↗
PubMed1991

In vivo DNA synthesis is not uniformly increased in arterial smooth muscle of young spontaneously hypertensive rats.

We compared the distribution of DNA synthesis over the arterial tree of young normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) with marginally elevated blood pressure. Six-week-old male SHR and WKY rats were therefore infused with 5-bromo-2'-deoxyuridine (BrdUrd) for 2 days and the nuclear incorporation of the thymidine analogue in the media of various arteries was determined by immunohistochemistry. In WKY rats, 2.5% of the arterial smooth muscle nuclei in elastic, muscular and resistance arteries incorporated BrdUrd. In SHR, DNA synthesis was more marked in large arteries than in resistance arteries. It was in addition significantly larger in the aorta, superior mesenteric, renal and femoral arteries of the SHR than in those of the WKY rats. However, nuclear incorporation of BrdUrd in vivo did not differ between SHR and WKY rats in aortic endothelium, carotid arterial smooth muscle, nor in mesenteric or renal resistance arteries. Between 6 and 20 weeks of age, the number of nuclear profiles per media cross-section did not increase in large arteries of WKY rats and SHR. During this period of time, however, carotid artery and thoracic aorta weight and DNA content increased. SHR large arteries gained more DNA than those of WKY rats. These data indicate that DNA synthesis is uniformly distributed over the arterial system in young WKY rats and that DNA synthesis is elevated in the smooth muscle of large arteries of 6-week-old SHR but not in their resistance arteries.

Animals↗
PubMed1991

Modification of circadian blood pressure and heart rate variability by five different antihypertensive agents in spontaneously hypertensive rats.

Effects of captopril, clonidine, hydralazine, metoprolol, and prazosin on the circadian variability of blood pressure (BP) and heart rate (HR) as well as on BP and HR rises at awakening were studied in spontaneously hypertensive rats (SHR). An on-line computerized system was used for continuous intraarterial (i.a.) recording of BP and HR. Drugs were infused intravenously (i.v.) with osmotic minipumps. Circadian BP patterns were more pronounced and variable in SHR than in Wistar-Kyoto normotensive control rats. HR patterns were similar in both groups. Antihypertensive treatment resulted in differential effects on the expression of the circadian BP and HR patterns in SHR. Reductions in BP variability and reductions in the awakening increase in BP were not correlated with the BP-lowering efficacy of agents. Treatment with clonidine reduced both circadian variability of BP and HR and the awakening increase. Prazosin reduced circadian BP variability and its awakening increase, whereas metoprolol reduced circadian HR variability only. Hydralazine and captopril did not cause any major effects on the circadian variability of BP and HR. These data indicate that circadian rhythms of BP and HR are under sympathetic control in SHR and are not influenced by nonsympatholytic vasodilators.

Animals↗
PubMed1991

Two weeks of intermittent dobutamine therapy restores cardiac performance and inotropic responsiveness in conscious rats with heart failure.

Dobutamine is frequently used for acute therapy in heart failure. In the present study, the hemodynamic effects of long-term intermittent dobutamine therapy were investigated in conscious rats with heart failure. Rats with healed myocardial infarctions received two i.p. injections of dobutamine per day for 2 weeks. Hemodynamic measurements were performed 90-180 min after the last injection. Two weeks of intermittent dobutamine significantly restored all hemodynamic changes induced by infarction. The maximal cardiac output during volume loading was depressed due to infarction and dose-dependently restored by 2 weeks of intermittent dobutamine. An increased stroke volume accounted for this improvement since the heart rate was not altered. In order to investigate changes in adrenergic responsiveness, the effects of acute dobutamine in nontreated and 2 weeks of dobutamine-treated infarcted rats were compared to those in control rats. Whereas chronotropic responses to acute dobutamine were comparable for all experimental groups, the inotropic response was reduced in nontreated infarcted rats but dose-dependently restored after 2 weeks of intermittent dobutamine therapy. From the data, we conclude that 2 weeks of intermittent dobutamine therapy in conscious rats with healed myocardial infarcts improved cardiac performance and restored the inotropic response to acute dobutamine administration. Data indicate that dobutamine has a long-term effect on cardiac function, which differs from the acute inotropic effect.

Animals↗
PubMed1991

Regional hemodynamic effects of rilmenidine and clonidine in the conscious spontaneously hypertensive rat.

Rilmenidine is an oxazoline analogue that has antihypertensive properties that resemble those of clonidine. Since rilmenidine has recently been described to have a relatively greater affinity for imidazoline receptors than clonidine, it was of interest to study whether this has functional consequences with regard to the regional hemodynamic responses. We investigated regional hemodynamics in conscious spontaneously hypertensive rats, equipped with miniature Doppler flow probes on the renal and mesenteric arteries and on the abdominal aorta. Clonidine (3-30 micrograms/kg) and rilmenidine (0.2-3 mg/kg) induced similar, dose-dependent reductions in heart rate. Both also induced an early hypertensive response, which was greater with rilmenidine, and similar later blood pressure reductions, which were maintained over 3 h. The early hypertensive response was associated with generalized vasoconstriction. Rilmenidine caused slightly greater mesenteric and hindquarter constriction than clonidine, whereas renal effects did not differ significantly. During the hypotensive phase, rilmenidine was a less potent mesenteric and hindquarter vasodilator than clonidine. During this phase, renal blood flow was at control levels, probably indicating autoregulation of renal flow. The minor differences in regional hemodynamic effects suggest that clonidine and rilmenidine can both be used as potent antihypertensives. The fact that rilmenidine has been suggested to possess less sedative side-effects suggests that, on this basis, it may be superior for antihypertensive drug therapy.

Animals↗
PubMed1991

Effects of angiotensin II and angiotensin converting enzyme inhibitors on contractile and growth responses in isolated carotid arteries of the rat.

We evaluated effects of inhibitors of angiotensin converting enzyme (ACE) on growth responses in isolated rat carotid arteries (CA) during continuous exposure to exogenous growth factors in vitro. In freshly isolated CA of adult Wistar-Kyoto rats (WKY) that had been denuded of endothelium, angiotensin-I (AT-I) and angiotensin-II (AT-II) induced concentration dependent contractions (1 nM to 1 microM). Captopril (100 microM) and lisinopril (10 microM) did not affect responses to AT-II, but increased the ED50 for AT-I 50-fold. To study the effects of ACE inhibition on arterial growth responses in vitro, we measured nuclear incorporation of the thymidine analogue, 5-bromo-2'-deoxyuridine (BrdUrd), during organoid culture of isolated CA segments in continuous presence of 20% calf serum. During 4 days of organoid culture 7-10% of the medial smooth muscle nuclei incorporated BrdUrd. During long-term culture (15 days) a new layer of cells developed at the adventitial border of the arterial segments. Continuous presence of captopril (10 microM to 100 microM) or lisinopril (1 microM to 10 microM) did not affect the extent of DNA synthesis in the media or in the newly formed cell layer. Unlike endothelin-1 (ET-1), exogenous AT-II did not stimulate DNA synthesis in isolated renal artery segments. These observations indicate the presence of ACE accessible to exogenous AT-I in arterial compartments other than the endothelium. Interference with this enzyme did not alter growth responses of the isolated arterial wall to serum. Since, in addition, exogenous AT-II did not stimulate intra-arterial DNA synthesis, effects of ACE-inhibitors on arterial growth responses in vivo are most likely due to an indirect effect.

Angiotensin I↗
PubMed1991

The microcirculation and essential hypertension.

Essential hypertension is characterized by a progressive increase of the mean arterial pressure paralleled by a concomitant increase in the total peripheral resistance. This elevated resistance is the consequence of (a) a decreased internal diameter, (b) an increased wall-to-lumen ratio or (c) a decreased number of small arteries or arterioles. A considerable part of the elevated vascular resistance is determined at the microcirculatory level. This paper reviews the studies performed to unravel the resistance-elevating mechanisms in the microvasculature of different tissues. Furthermore the possible role of the microcirculation in the pathogenesis of essential hypertension is discussed.

Animals↗
PubMed1991

Angiotensin I converting enzyme inhibitors and cardiac remodeling.

Angiotensin I converting enzyme (ACE) inhibitors are widely used in the treatment of heart failure. It is not known whether the beneficial effects of ACE inhibition are only due to a reduction in pre- and afterload or whether ACE inhibition also has direct effects on cardiac remodeling processes after myocardial infarction. In addition, the effects of differential timing of the treatment are not known. The left coronary artery was ligated in rats to induce a myocardial infarction. Control rats received no treatment. Captopril was given via s.c. placed minipumps (500 micrograms/kg.h) in the first 3 weeks or in the third and fourth week after induction of the myocardial infarction. The structural changes of the heart were investigated. Early after ligation the left ventricle was dilated in association with a marked, but transient DNA synthesis in the remaining left ventricle; the amount of collagen also increased. Early captopril treatment blocked this response, while late treatment had no effects. We suggest that the negative effects of early captopril treatment are due to an interference with the normal adaptive responses of the heart to the loss of muscle, probably through interactions at the cellular level.

Adaptation, Physiological↗
PubMed1990

Beneficial hemodynamic effects of two weeks' milrinone treatment in conscious rats with heart failure.

Milrinone is a phosphodiesterase inhibitor which combines vasodilating effects with inotropic effects. Hemodynamic improvement after acute administration and increased survival with chronic milrinone therapy in rats with heart failure have been reported before, and suggest long-term hemodynamic improvement. However, no detailed hemodynamic studies are available on prolonged milrinone therapy in rats with heart failure. Therefore, the hemodynamic effects of 2 weeks' milrinone therapy were now investigated in conscious rats with heart failure due to myocardial infarction. The effects were compared to hemodynamic changes after acute administration. Acute milrinone increased the baseline cardiac output in infarcted rats by increasing heart rate rather than stroke volume. However, the maximal cardiac output achieved when the heart was stimulated through a volume load was improved due to increased stroke volume as well as increased heart rate. The increase in maximally stimulated cardiac output after acute milrinone was found to be related to infarct size. Two weeks' milrinone therapy in chronically infarcted rats dose dependently restored the hemodynamic changes which were caused by infarction. In contrast to acute administration, two weeks' milrinone restored cardiac function without an increase in heart rate. The effects were achieved at a rate of administration which presumably has no acute inotropic effects. The data indicate that acute milrinone in infarcted rats has vasodilating effects. Positive inotropic effects, possibly masked by concomitant venodilatation at baseline conditions, became overt after stimulation by volume loading. Long-term milrinone dose dependently restored cardiac function in infarcted rats without effects on heart rate or mean arterial pressure, suggesting that different mechanisms may be involved.

Animals↗