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H Buikema

Publications and source records attributed to H Buikema.

33 records · Page 2Linked to original sources
PubMed1997

Cardiovascular end-organ damage in Ren-2 transgenic rats compared to spontaneously hypertensive rats.

To compare hypertensive end-organ damage in two genetic forms of hypertension we assessed cardiovascular function in two rat strains of genetic hypertension: transgenic rats overexpressing the mouse Ren-2 gene [(TGR(mREN2)27]) and blood pressure matched spontaneously hypertensive rats (SHR). Despite similarly elevated blood pressure, systolic dp/dt (mmHg/s) was more impaired in transgenic rats (3099 +/- 446) than in SHR (3571 +/- 272) and normals (4342 +/- 119; P < 0.05). Left ventricular weight (mg/g body weight) increased more in the transgenic rats (40 +/- 3) than in SHR (31 +/- 2) and normals (26 +/- 2). Endothelium-dependent relaxation was significantly decreased only in the transgenic rats. This study shows significantly more cardiac and endothelial dysfunction in transgenic, hypertensive TGR (mREN2)27 than in age and blood pressure matched SHR. This supports the hypothesis that chronic activation of the renin-angiotensin system significantly contributes to hypertensive end-organ damage.

Animals↗
PubMed1997

Dyslipidemia and endothelium-dependent relaxation in internal mammary arteries used for coronary bypass surgery.

OBJECTIVE: Impairment of endothelium-dependent relaxation is related to dyslipidemia and may be an early marker for atherosclerosis in angiographically smooth arteries. The aim of the present study was to relate preoperative serum lipids to endothelium-dependent relaxation in internal mammary arteries of patients undergoing coronary bypass surgery. METHODS: The study group consisted of 37 patients, from whom segments of the internal mammary artery were obtained during surgery. Measurements of endothelium-dependent relaxation were performed in organ baths by adding methacholine (10 nM-10 microM). RESULTS: All internal mammary arteries dilated in response to methacholine, ranging from 4 to 112% of the precontraction to 10 mumol phenylephrine. In a multiple regression model, increased total serum cholesterol appeared to be the best predictor for impaired endothelium-dependent relaxation. A 1 mmol increase of total cholesterol was associated with a 11.2% decrease of endothelium-dependent relaxation (P = 0.006). When total cholesterol was omitted from the model, LDL-cholesterol became the best predictor of endothelium-dependent relaxation (regression coefficient 10.3%/mmol; P = 0.02). No other variable was significantly associated with endothelium-dependent relaxation, and none of the preoperative variables was associated with endothelium-independent relaxation, expressed as the response to sodium nitrite (10 mM). CONCLUSION: Our study showed that endothelium-dependent relaxation in apparently non-diseased internal mammary arteries used for coronary bypass surgery was independently related to preoperative (LDL)-cholesterol levels.

Adult↗
PubMed1997

Early pharmacologic intervention may prevent the deterioration in endothelial function after experimental myocardial infarction in rats: effects of ibopamine and captopril.

BACKGROUND: Endothelial function is progressively disturbed after myocardial infarction (MI), which may be related to both neurohumoral activation and hemodynamic alterations. Consequently, it may be suggested that drugs that favorably affect these factors may also have a positive effect on endothelial function. METHODS AND RESULTS: Rats underwent coronary ligation (n = 24) or remained unoperated (n = 21), and were randomized to captopril (25 mg/kg/d) or ibopamine (10 mg/kg/d) or remained untreated. Treatment was started following MI and lasted 8 weeks, after which rats were sacrificed for in vitro studies. Left ventricular end-systolic pressure was higher in rats treated with captopril (83 +/- 6 mmHg) and ibopamine (80 +/- 3 mmHg), as compared with untreated MI rats (48 +/- 6 mmHg, P < .01 for both). Increased plasma norepinephrine levels in MI rats were reduced by captopril and ibopamine (both P < .05). Infarct size was smaller in rats treated with captopril (26.7 +/- 3.6%, P < .05) and ibopamine (31.4 +/- 4.3%, P = NS), as compared with untreated rats (41.7 +/- 2.4%). Maximal endothelium-dependent relaxation (Emax; % precontraction) and the concentration of methacholine causing 50% Emax, expressed as negative log(pIC50) were significantly reduced in aortic rings from MI control subjects (pIC50 = 6.15 +/- 0.06 mol/L, Emax = 32.0 +/- 4.2%), as compared with normal control subjects (pIC50 = 6.57 +/- 0.07 mol/L, P < .001; Emax = 50.0 +/- 4.9%, P = .022). Captopril (pIC50 = 6.30 +/- 0.08 mol/L, Emax = 45.1 +/- 7.0%) and ibopamine (pIC50 = 6.60 +/- 0.08 mol/L, Emax = 43.8 +/- 5.2%) improved these parameters in MI rats. CONCLUSION: The results demonstrate preservation of endothelial function by early pharmacologic intervention after experimental MI in rats in the setting of concomitant reduction in infarct size.

Animals↗
PubMed1997

Differential inhibition of plasma versus tissue ACE by utibapril: biochemical and functional evidence for inhibition of vascular ACE activity.

Utibapril is an angiotensin-converting enzyme (ACE) inhibitor with a proposed tissue-specific inhibitory profile. This implies that at a certain dose, utibapril should be able to inhibit tissue ACE activity without affecting plasma ACE. Moreover, if tissue ACE activity is rate limiting, functional conversion of angiotensin I should be decreased. Accordingly, we studied the dose-dependent effect of long-term treatment with utibapril on plasma and tissue ACE. Normal Wistar rats were randomly allocated to oral treatment with different doses of utibapril (0, 2, 10, 50, or 250 micrograms/kg/day) for 30 days. Tissue inhibition of ACE was assessed biochemically, whereas functional conversion of angiotensin I was determined in the isolated organ. Utibapril significantly inhibited plasma, renal, and vascular ACE but not ventricular ACE activity. Notably, however, only treatment with the highest dose of utibapril resulted in a significant inhibition of plasma ACE, whereas vascular ACE activity was already significantly inhibited after treatment with a lower dose of utibapril. In accordance, utibapril dose-dependently inhibited the contraction of isolated aortic rings to angiotensin I. Furthermore, angiotensin I-induced decreases in coronary flow in the isolated heart were significantly inhibited after treatment with the higher doses of utibapril. These data suggest the preferential inhibition of vascular ACE by utibapril in normal rats. Furthermore, the dose-dependent inhibition of the functional conversion of angiotensin I indicates that the tissue ACE activity may be rate limiting in vascular beds in rats.

Angiotensin I↗
PubMed1997

Effects of amlodipine on endothelial function in rats with chronic heart failure after experimental myocardial infarction.

In chronic heart failure, the role of endothelial dysfunction is not yet well established. As calcium metabolism plays an important role in the endothelium, it might be suggested that calcium channel blockers influence endothelial function. Although calcium channel blockers are generally contraindicated in chronic heart failure, because they are believed to stimulate neurohumoral mechanisms and to exert negative inotropic effects, recently it has been suggested that amlodipine might have a favorable affect on mortality in patients with heart failure. The mechanism of amlodipine that contributes to this beneficial effect is not known. Therefore we investigated whether 10 weeks of amlodipine treatment could influence endothelial function in rats with congestive heart failure induced by myocardial infarction. The main finding of our study was that amlodipine, when administered for 10 weeks to rats after a myocardial infarction had been induced, had no significant effects on in vitro and in vivo hemodynamics or neurohormones. The effect of amlodipine on endothelium-intact, norepinephrine-precontracted aortic rings appears to differ from the placebo treatment with respect to the endothelium-dependent relaxation, whereas no differences are seen in endothelium-independent relaxation. We conclude that our data do not support a beneficial role of amlodipine on endothelial function in chronic heart failure.

Amlodipine↗
PubMed1997

The renin-angiotensin system and vascular function. The role of angiotensin II, angiotensin-converting enzyme, and alternative conversion of angiotensin I.

The renin-angiotensin system has been implicated in vascular function and disease. Angiotensin-converting enzyme and angiotensin II are believed to be the most important components. However, alternative factors, such as angiotensin-I/II-(1-7) and chymase, have also been shown to be of significance in animal models. In this paper, we review some facts and provide additional proof for the functional significance of angiotensin-I/II-(1-7) and chymase in humans.

Angiotensin I↗
PubMed1996

Activated tissue renin-angiotensin systems add to the progression of heart failure.

In this paper, we review the hypothesis that activated tissue renin-angiotensin systems play a detrimental role in heart failure. The main arguments for this idea are discussed: a) tissue renin-angiotensin systems behave functionally distinct from the circulating renin-angiotensin system; b) tissue renin-angiotensin systems are activated in heart failure; c) activated tissue renin-angiotensin systems induce cardiovascular dysfunction. Finally, this hypothesis predicts that optimal treatment in heart failure requires the inhibition of tissue renin-angiotensin systems. However, studies pertaining to this prediction are still lacking, particularly in human subjects.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

The deletion polymorphism of the angiotensin-converting enzyme gene is related to phenotypic differences in human arteries.

We hypothesized that angiotensin-converting enzyme (ACE) insertion/deletion polymorphism may be related to arterial phenotypic differences that could explain the adverse effects of deletion polymorphism. Accordingly, contractile responses to angiotensin I and II (0.1 nmol.1(-1)-1 micromol.1(-1), endothelium-dependent relaxation to methacholine (0.01-100 micromol.1(-1), and the effect of NG-monomethyl-L-arginine (L-NMMA; 100 micromol.1(-1) on phenylephrine (10 micromol.1(-1) induced contraction, were studied in isolated rings of internal mammary arteries obtained from patients undergoing coronary bypass surgery. The results were analysed according to the ACE genotype of the patient (II, n = 8; ID, n = 11; DD, n = 9) as well as the presence/absence of either allele. The arteries from patients with the D allele (ID/DD) displayed a lower sensitivity to methacholine (P < 0.05 vs II), which suggested that the capacity of the endothelium for nitric oxide release in response to stimulation was also lower. By contrast, the increase in phenylephrine-induced contraction, by pre-incubation with L-NMMA, was more pronounced in the group with the DD allele (31 +/- 5%) than with the ID (11 +/- 11%) and II alleles (1 +/- 11%, P < 0.05 vs DD), which suggested a higher level of basal nitric oxide release. Finally, the differences in the responses to angiotensin I and II, which were used to evaluate the vascular conversion of angiotensin I, indicated that the level of angiotensin I conversion was higher in patients with the D allele (ID/DD, P < 0.05 vs II). The findings of this study indicate that ACE insertion/deletion polymorphism is related to arterial phenotypic differences in endothelial function and angiotensin I conversion.

Angiotensins↗
PubMed1995

Hyperactive tissue renin-angiotensin systems in cardiovascular dysfunction: experimental evidence and clinical hypotheses.

In this review, hypotheses are discussed with regard to the role of local, tissue renin-angiotensin systems in the progression of cardiovascular dysfunction. After local renin-angiotensin systems had been described as functionally distinct systems, recent experimental studies have suggested an association between hyperactivity of these local renin-angiotensin systems, and cardiovascular dysfunction. Moreover, the existence of these local renin- angiotensin systems has been confirmed in humans, and early data indicate that the human cardiac renin-angiotensin system may be activated in heart disease. Furthermore, polymorphisms in genes coding for the renin-angiotensin system seem associated with hypertension and left ventricular hypertrophy. These observations may be clinically relevant as inhibition of local renin-angiotensin systems may be an important prerequisite to obtain an optimal clinical effect.

Animals↗
PubMed1994

Neurohumoral and hemodynamic effects of ibopamine in a rat model of chronic myocardial infarction and heart failure.

There is increasing evidence that both neurohumoral and hemodynamic factors play a role in disease progression in chronic heart failure (CHF). To examine the influence of the oral dopamine agonist ibopamine on these factors, we studied 20 rats with chronic myocardial infarction and CHF, and compared them with 20 normal rats. After 6 weeks, rats were randomly divided between control treatment (50%) or ibopamine (50%) for 3 weeks. At the end of the study, plasma and tissue neurohumoral parameters, as well as hemodynamics, were determined. In infarcted rats, the elevated plasma norepinephrine (PNE) levels were reduced by ibopamine (251 +/- 19 vs. 138 +/- 32 pg/ml; p < 0.05). Other plasma neurohormones measured (epinephrine, renin, aldosterone, and angiotensin converting enzyme [ACE]) were not significantly increased in rats with myocardial infarction and were not affected by ibopamine. Cardiac (tissue) ACE was increased in infarcted rats (12.1 +/- 1.9 U/l/min) and was significantly lowered by ibopamine (9.6 +/- 1.0 U/l/min; p < 0.05); renal ACE was unaffected. Blood pressure and heart rate were similar in the two groups and were not influenced by ibopamine treatment. In conclusion, in chronic myocardial infarction and CHF in rats, ibopamine reduces the elevated levels of PNE and cardiac ACE. Further research will be needed to determine whether this effect may lead to a favorable influence on disease progression in CHF.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Effect of ibopamine on ventricular remodeling after experimental myocardial infarction: a comparison with captopril.

Remodeling after myocardial infarction (MI) is influenced not only by hemodynamic but possibly by neurohumoral factors as well. Ibopamine is an orally active dopamine agonist (DA) with both hemodynamic and neurohumoral properties in humans. The latter property prevails in rats. To study the dose-dependent effect of ibopamine on myocardial remodeling and compare it with the effect of captopril, we randomized rats with (n = 27) or without (n = 27) experimental MI to captopril (25 mg/kg/day), low-dose ibopamine (10 mg/kg/day), high-dose ibopamine (30 mg/kg/day), or no treatment. After 8-week treatment, hearts were isolated and left ventricular (LV) function, LV cavity volume, and infarct size (IS) were evaluated. Both ibopamine and captopril significantly reduced plasma norepinephrine (NE) levels in rats with MI. In untreated but not in treated infarcted rats, LV function was significantly reduced as compared with that of controls. IS was reduced in all three active treatment groups as compared with untreated rats. LV cavity volume was significantly increased in untreated rats with MI as compared with controls. This dilatation was attenuated by both ibopamine and captopril. Ibopamine, comparable to captopril, administered early after coronary ligation reduced IS and subsequent ventricular dilatation, resulting in preservation of cardiac function in this rat model. This observation suggests a major role for neurohumoral activation in the process of remodeling.

Animals↗
PubMed1993

The effect of cholesterol reduction on the endothelial function and progression of atherosclerosis in WHHL rabbits.

In 3-month-old homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits the effect of treatment with the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor pravastatin was studied for 9 months and related to the endothelial function of the coronary arteries of isolated hearts and rings of the distal abdominal aorta. Oral administration of pravastatin in doses up to 40 mg/kg per day significantly decreased plasma cholesterol by 51% in comparison to untreated WHHL rabbits. Basal coronary flow and bradykinin-induced increase in coronary flow in Langendorff hearts of the pravastatin-treated animals were significantly greater than the flow in the control animals, whereas the metacholine-induced relaxation of abdominal aortic rings was not different and attenuated in comparison to New Zealand white rabbits. The incidence of atherosclerotic lesions in four main coronary arteries and the aorta was significantly lower in the pravastatin treated animals (25.0% and 52.8% respectively) than in untreated WHHL rabbits (34.1% and 80.0% respectively). The mean percentage of narrowing in the aorta was also significantly lower in the pravastatin-treated group (12.0%) than in the controls (25.2%). Significant correlations were found between the extent of atherosclerotic lesions and the bradykinin-induced increase in coronary flow versus plasma total cholesterol levels. Thus, in this model, long term cholesterol lowering treatment with pravastatin starting at an early age retards the progression of plaque formation and preserves the endothelium-dependent relaxation of the coronary arteries.

Animals↗
PubMed1993

Endothelium dependent relaxation in two different models of chronic heart failure and the effect of ibopamine.

OBJECTIVES: The purpose was to relate endothelium dependent relaxation to neurohumoral and haemodynamic changes in rats with chronic heart failure. METHODS: Rats were submitted to either coronary ligation causing myocardial infarction or banding of the abdominal aorta (aortic stenosis), and comparisons were made with normal rats (n = 20 per group). Starting six weeks after surgery, half of the experimental animals received ibopamine and the other half served as controls and were given saline for another three weeks. After this, haemodynamic and neurohumoral variables were determined and the rats were killed. Rings of both the thoracic and abdominal aorta were studied in organ baths to measure their response to vasoactive agents. RESULTS: Increased plasma noradrenaline concentrations in rats with myocardial infarction and aortic stenosis were reduced by ibopamine. Blood pressure and heart rate, which were higher in rats with aortic stenosis than in rats with myocardial infarction and in normal rats, were unaffected by ibopamine. The maximal relaxation to sodium nitrite was depressed in the thoracic aorta from rats with myocardial infarction. The pIC50 of metacholine induced relaxation was smaller in the thoracic aorta from rats with myocardial infarction and aortic stenosis. By contrast, both pIC50 and the maximal relaxation (Emax) were increased in the abdominal aorta from rats with aortic stenosis, whereas Emax was smaller in rats with myocardial infarction. Ibopamine had no significant effects on these responses. CONCLUSIONS: Endothelium dependent relaxation to metacholine was selectively altered in rats with chronic heart failure due to aortic stenosis, probably because of differences in regional haemodynamics. In rats with myocardial infarction, however, endothelium dependent relaxation was impaired in both the thoracic and abdominal aorta. Ibopamine acted as a neurohumoral modulator by reducing increased noradrenaline concentrations but had no significant effect on either endothelium dependent or independent relaxation.

Animals↗
PubMed1992

Differences in vasomotor control between human gastroepiploic and left internal mammary artery.

BACKGROUND: Internal mammary artery grafts have a greater long-term patency rate than do saphenous vein grafts. This has in part been attributed to the difference in endothelial function of arterial and venous vessels. The use of the gastroepiploic artery in coronary artery bypass grafting has become popular recently because of its similarity to internal mammary artery. In this study, we compared the endothelial responses of gastroepiploic and left internal mammary arteries to vasoactive substances. METHODS AND RESULTS: Gastroepiploic and left internal mammary arteries were obtained during surgery from patients undergoing elective coronary artery bypass surgery. Vascular rings of both graft types were studied in organ bath experiments. Relaxation responses to metacholine and sodium nitrite were similar in rings of both arteries. In contrast, bradykinin induced potent relaxations in rings of the gastroepiploic artery but not in rings of the left internal mammary artery. Furthermore, there was a inverse correlation of maximal metacholine-induced relaxations with increasing age. CONCLUSIONS: The resemblance of relaxations induced by metacholine and sodium nitrite in both gastroepiploic and left internal mammary arteries suggests a similar activation and behavior of the L-arginine pathway in both arteries. The difference in bradykinin-induced relaxations may reflect a prostaglandin metabolism in the gastroepiploic artery different from that in the left internal mammary artery. Furthermore, maximal metacholine-induced relaxation in rings of the left internal mammary artery shows an age dependency that was not observed in rings of the gastroepiploic artery.

Arteries↗