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H van Essen

Publications and source records attributed to H van Essen.

34 records · Page 2Linked to original sources
PubMed1986

Target organ directed drug delivery: evaluation of renal infusion of chromium-51 ethylenediaminetetraacetate and sodium o-[125I]iodohippurate in the Wistar Kyoto rat.

To evaluate the merits of intrarenal drug delivery, the disposition of chromium-51 ethylenediaminetetraacetate (51Cr EDTA) and sodium o-[125I]iodohippurate (125I OIH) was studied following their constant-rate infusion into either the jugular vein or the left or right renal artery of Wistar Kyoto rats. The contralateral kidney was removed. Renal blood flow through the lateral kidney was measured during the experiment via an electromagnetic flow probe. Urine and systemic arterial blood samples were taken at steady state. The clearance and extraction of both substances by the right kidney were independent of the route of administration. Nonlinear kinetics were observed during infusion of 125I OIH at the highest infusion rate in the left kidney. At steady state the advantage of intrarenal over systemic delivery was limited because of the relative high blood flow of the kidney. Only a small reduction (30%) in systemic concentration was achieved by infusion of 51Cr EDTA. Intrarenal infusion of the lower dose (10 nCi/min) of 125I OIH reduced the systemic concentration by greater than 80% when compared with systemic infusion. Intrarenal infusion of the higher dose (40 nCi/min) saturated elimination processes in parts of the left kidney because of nonhomogeneous flow distribution.

Animals↗
PubMed1986

Role of baroreflex activation in the regional hemodynamic effects of the beta-blockers tertatolol and propranolol in conscious spontaneously hypertensive rats.

The effects of the beta-adrenoceptor-blocking drugs tertatolol and propranolol on regional hemodynamics were compared in intact and sinoaortic denervated (SAD) conscious spontaneously hypertensive rats (SHR). Miniaturized Doppler flow probes were used for the continuous determination of changes in flows and resistances in the renal, mesenteric, and hindquarter vascular beds. In intact animals 5 mg/kg propranolol i.v. caused an initial increase and a later gradual fall in mean arterial blood pressure (MAP) and an early rise in all three resistances. In SAD rats the reduction in MAP occurred more readily and no increases in RR and MR were observed. RR even decreased significantly. 0.5 mg/kg tertatolol i.v. caused a similar change in MAP as did propranolol. In contrast, tertatolol increased resistance only in the hindquarter vascular bed, both in intact and SAD animals. These data show an important role of sinoaortic baroreflex activation in the early peripheral vasoconstriction caused by propranolol in conscious SHR. Moreover, the data suggest that tertatolol inhibits the sympathetic nervous system-mediated reflex vasoconstriction.

Adrenergic beta-Antagonists↗
PubMed1985

Effects of the renal vasodilator prodrug CGP 22 979A and its parent compound CGP 18 137A on renal and central hemodynamics in conscious spontaneously hypertensive rats.

In a previous study we reported that the renal prodrug CGP 22 979A (N-acetyl-L-glutamic acid-N-[N2-(5-n-butyl-2-pyridyl)-hydrazide) causes selective renal vasodilation in conscious spontaneously hypertensive rats (SHR) in doses up to 10 mg/kg. The hydralazine-like parent compound CGP 18 137A (2-hydrazino-5-n-butyl-pyridine) causes general vasodilatation. In the present study we report on renal hemodynamics, excretion of water and sodium and central hemodynamic effects of CGP 18 137A and CGP 22 979A in conscious, unrestrained SHR. CGP 18 137A (1 mg/kg) reduced effective renal plasma flow [measured as plasma clearance of [125I]p-aminohippuric acid] and glomerular filtration rate (measured as plasma-clearance of 51Cr-EDTA), in the first hour after injection. CGP 22 979A (3-30 mg/kg) dose-dependently increased effective renal plasma flow, but not glomerular filtration rate thus reducing filtration fraction. In spite of the lack of increase of glomerular filtration rate, CGP 22 979A increased excretion of sodium and water in a separate group of SHR. CGP 18 137A reduced renal excretory function slightly. In another group of conscious SHR we studied the effects of CGP 18 137A and CGP 22 979A on central hemodynamics. These animals had an electromagnetic flow-probe on the ascending aorta, to measure cardiac output (CO). Mean arterial pressure was measured from a chronic catheter in the abdominal aorta. Total peripheral resistance (TPR) and stroke volume were calculated. CGP 18 137A (0.3-1 mg/kg) reduced mean arterial pressure and TPR whereas CO increased immediately after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Haemodynamic effects of bromocriptine in the conscious spontaneously hypertensive rat.

The systemic haemodynamic effects of 0.3 mg kg-1 bromocriptine s.c. in conscious, chronically instrumented spontaneously hypertensive rats (SHR) has been investigated. Bromocriptine caused a gradual, long-lasting significant fall in mean arterial pressure with a maximum of 26 +/- 3 mmHg (-17%). The fall was related to a significant decrease in stroke volume index (-9 +/- 2 microliters 100 g-1; -10%) and cardiac index (-3.9 +/- 0.8 ml min-1 100 g-1; -12%). No significant changes in heart rate or total peripheral resistance index were observed. These data do not support previous suggestions that the antihypertensive effect of bromocriptine is caused by inhibition of the release of vasopressor substances. It is suggested that bromocriptine causes a reduction of venous return of the blood to the heart, possibly related to intrarenal effects.

Animals↗
PubMed1984

Evaluation of renal function during intrarenal norepinephrine infusion in conscious rats.

Previous studies have shown that intrarenal infusion of norepinephrine (NE) causes acute renal failure in anesthetized dogs and rats. We hypothesized that anesthesia prevents the kidney of escaping from the ischemic insult. In this paper, we report measurements of renal function parameters during acute as well as during chronic intrarenal NE infusion in conscious freely moving rats. Intrarenal NE application in doses of 4 and 36 micrograms/kg X h was performed via the suprarenal artery by means of subcutaneously implanted minipumps. During acute intrarenal NE infusion over a 2-hour period in anesthetized as well as conscious rats, renal blood flow (RBF) was determined by means of the pulsed Doppler flowmeter technique. During long-term NE administration for 5 days, glomerular filtration rate (GFR) was determined as clearance of 51Cr-EDTA and effective renal plasma flow (ERPF) as clearance of 125I-hippuric acid. Clearance measurements were performed on control day, and on the 1st and 4th day of intrarenal NE infusion; furthermore, on the 1st and 4th day after stopping the intrarenal NE infusion. Acute intrarenal administration of doses of NE higher than 12 micrograms/kg X h, in anesthetized rats immediately reduced RBF to zero levels. However, in conscious rats, neither acute nor chronic intrarenal NE application induced severe long-lasting reductions in GFR or RBF respectively ERPF at any dose of NE applied. Therefore, we conclude that no acute renal failure is induced during intrarenal NE infusion in conscious rats; this is probably due to protective neurogenic mechanisms which are relatively inactivated during pentobarbital anesthesia.

Acute Kidney Injury↗
PubMed1984

Calcium antagonists: systemic and regional haemodynamic effects in conscious spontaneously hypertensive rats (SHR).

The systemic and regional (renal, mesenteric and hindquarter) haemodynamic effects of the calcium antagonists verapamil, nifedipine and PY 108-068 [diethyl 4-(2, 1, 3-benzoxadiazol-4-yl)-1, 4-dihydro-2, 6-dimethylpyridine-3, 5-dicarboxylate] were studied in conscious, chronically instrumented spontaneously hypertensive rats (SHR). All three calcium antagonists caused a dose-dependent fall in mean arterial pressure (MAP) and total peripheral resistance. In intact animals the fall in resistance was related primarily to a vasodilatation in the hindquarter (mainly muscular) vascular bed. During the early fall in blood pressure a reflex rise in cardiac output and heart rate was observed following nifedipine and PY 108-068, but not after verapamil. Following sinoaortic baroreflex denervation the dose-response curve for the calcium antagonist-induced fall in blood pressure and total peripheral resistance was shifted to the left. Moreover, the calcium antagonists then caused a comparable degree of vasodilation in all three vascular beds studied. It is concluded that calcium antagonists preferentially dilate the muscular bed in intact animals; however, sinoaortic baroreflex denervation unmasks an unselective pattern of vasodilatation.

Animals↗
PubMed1983

Hemodynamic effects of the arteriolar vasodilators hydralazine, dihydralazine and endralazine in the conscious spontaneously hypertensive rat.

The hemodynamic effects of the vasodilators hydralazine, dihydralazine and endralazine were studied in conscious, unrestrained spontaneously hypertensive rats (SHR) equipped for chronic hemodynamic measurements. The arteriolar vasodilators hydralazine (0.3 mg/kg i.a.) and dihydralazine (0.3 mg/kg i.a.) caused a rapid fall in blood pressure and peripheral resistance, lasting up to 24 h in the case of dihydralazine. Immediately after injection, the cardiac output and heart rate were increased significantly. These effects only lasted for 1-2 h. The hemodynamic pattern of the new vasodilator endralazine (0.1-1 mg/kg i.a.) was very similar, with a duration of action similar to that of dihydralazine. The role of baroreceptor reflexes in the early hemodynamic effects of vasodilators was studied by comparing the effects of 0.3 mg/kg hydralazine in baroreflex-denervated and non-denervated SHR. The decrease in blood pressure and peripheral resistance was significantly larger in the denervated SHR, whereas increases in cardiac output and heart rate were almost completely absent in these animals. These data suggest that baroreceptor reflexes oppose the early fall in blood pressure and peripheral resistance induced by vasodilators. However, the activity of the baroreflex seems of very short duration, suggesting a rapid adaptation to the prevailing blood pressure. Moreover, the data show that endralazine is an effective arteriolar vasodilator in conscious SHR.

Animals↗
PubMed1983

Chronic local infusion into the renal artery of unrestrained rats.

A method is described for providing chronic access to the right renal artery of unrestrained rats. It consists of insertion of a very thin (OD 0.2 mm) catheter into the right suprarenal artery of Wistar rats. The suprarenal artery originates from the right renal artery. After the cannula has been guided subcutaneously to the neck, it is connected to an Alzet osmotic minipump. The method has a success ratio of over 90% for periods up to 14 days. In the present study, we investigated the effects of catheter implantation on renal hemodynamics in uninephrectomized rats that were infused with saline for 2, 6, or 14 days. Values were compared with those obtained in control rats. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were estimated from plasma clearances of 51Crethylenediaminetetraacetic acid and 125I-p-aminohippuric acid, respectively. Mean arterial pressure was between 107 +/- 2 and 116 +/- 2 mmHg in all animals. Neither GFR nor ERPF was influenced by catheter implantation. It is concluded that the method does not interfere with renal function.

Animals↗
PubMed1983

Hemodynamic actions of diuretic agents.

The blood pressure lowering effect of diuretics in hypertensive disease is well documented. The hemodynamic actions underlying this antihypertensive effect differ in the early phase from the effects observed during long-term treatment. This article first describes new experiments on the hemodynamic effects of three diuretics, viz. hydrochlorothiazide, chlorthalidon and furosemide in conscious, chronically instrumented spontaneously hypertensive rats. This animal model was chosen in view of its good applicability for the study of the hemodynamics of antihypertensive drug action. Results show a marked early fall in stroke volume and cardiac index with all three diuretics. Mean arterial blood pressure was decreased only after a delay of several hours, because of an early large increase in total peripheral resistance. This article furthermore discusses possible mechanisms involved in the long-term return of peripheral resistance close to or below pre-treatment values. On the basis of data in the literature it is concluded that adaptation of baroreceptor reflexes, auto-regulatory responses of the peripheral vascular resistance and enhanced production of endogeneous vasodilator substances play an increasingly important role during the long-term hemodynamic actions of diuretic agents.

Animals↗
PubMed1980

Is the antihypertensive effect of propranolol caused by an action within the central nervous system?

Propranolol in doses from 0.01 to 5 mg/kg x day was infused intracerebroventricularly (i.c.v.) in conscious unrestrained spontaneously hypertensive rats during 5 days by using Alzet osmotic minipumps. When given by this route, brain concentrations achieve values that are approximately 100-fold higher than those after s.c. infusion of equal doses, whereas plasma-levels are comparable. In this study we compared the dose needed to lower blood pressure upon i.c.v. infusion with the dose of 5 mg/kg x day dl-propranolol, which we reported earlier to induce a long lasting bradycardia and antihypertensive effect when infused s.c. Vehicle, 0.01 and 0.1 mg/kg x day of dl-propranolol, did not have any effect on mean arterial pressure or heart rate. Infusion (i.c.v.) of 1 mg/kg x day lowered heart rate during the first 4 days of the infusion. On the fifth day, this effect had disappeared. Also, during the first 2 days of the infusion a reduction of mean arterial pressure was observed, but thereafter pressure was at control levels. Infusion of 5 mg/kg x day of dl-propranolol reduced heart rate significantly from the first day of infusion throughout the whole infusion-period. On the other hand, mean arterial pressure was lowered with a delay of 1 day. It remained significantly below control values throughout the rest of the experimental period. d-Propranolol in a dose of 5 mg/kg x day i.c.v. did not have any effects. Since upon i.c.v. infusion the dose needed for a blood pressure lowering effect is the same as that needed for a s.c. infusion, in spite of 100-fold higher brain-levels, it is concluded that the antihypertensive effect of propranolol in spontaneously hypertensive rats is not caused by an action of the drug in the central nervous system.

Animals↗
PubMedDate not supplied

Alpha-adrenergic reactivity of the microcirculation in conscious spontaneously hypertensive rats.

The goal of this study was to determine the functional distribution of alpha 1- and alpha 2-adrenoceptors in the striated muscle microcirculation. Experiments were performed in intact conscious spontaneously hypertensive rats (SHR) that were provided with a dorsal microcirculatory chamber to allow microvascular diameter measurements. Administration of selective alpha 1- and alpha 2-agonists, phenylephrine and azepexole, respectively, induced different patterns of microvascular constriction. alpha 1-Adrenoceptor stimulation showed a preferential constriction of large arteries and venules. The entire arteriolar microvasculature was sensitive to alpha 2-adrenoceptor stimulation, whereas the venular vessels did not respond to azepexole. The selective alpha 1- and alpha 2-antagonists prazosin and yohimbine showed patterns of vasodilator activity comparable to those of the corresponding agonists. The specificity of the drug-induced effects was verified by comparing their effects with those of graded hemorrhage, a non-pharmacological method for blood pressure lowering. In the range of blood pressure decreases comparable to that obtained by alpha-adrenoceptor antagonists, graded hemorrhage did not influence microvascular diameters. These results show a differential functional distribution of alpha 1- and alpha 2-adrenoceptors along the microvascular tree in striated muscle of conscious SHR.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

Antihypertensive effect of propranolol in conscious spontaneously hypertensive rats: central hemodynamics, plasma volume, and renal function during beta-blockade with propranolol.

In order to obtain a better insight into the hemodynamic changes during beta-blockade, we measured central hemodynamics, plasma volume, and renal function during both acute and long-term beta-blockade in conscious spontaneously hypertensive rats (SHR). Acutely, both 1 and 5 mg/kg propranolol immediately decreased heart rate (HR) and cardiac output (CO). However, total peripheral resistance (TPR) rose sharply, thus preventing mean arterial pressure (MAP) from falling during the first hours after injection. After 4 h TPR had returned to control values and, because CO was still reduced, MAP was lowered. This decrease of MAP persisted for more than 20 h. During 5-day infusion of propranolol (5 mg/kg/day) CO fell on the 1st day and remained lowered during the 5-day period. MAP was lowered from the second day onward. Despite the reduced CO and MAP, plasma volume (PV) did not increase during the 5-day infusion. Acute injection of 5 mg/kg/day did, however, result in a decreased PV at 1 h postinjection. In this time span central venous pressure remained unchanged. Quantitation of water and sodium excretion revealed an immediate diuresis and natriuresis after acute administration of propranolol. This occurred despite a reduced glomerular filtration rate and effective renal plasma flow, as quantitated by indicator clearance methods. We conclude that propranolol reduced tubular sodium reabsorption, possibly through blockade of tubular beta-receptors. This effect may be essential for the long-term antihypertensive efficacy of beta-blockers because it prevents sodium and water retention in a state of reduced MAP and CO.

Animals↗
PubMedDate not supplied

Hemodynamic characterization of hypertension induced by chronic intrarenal or intravenous infusion of norepinephrine in conscious rats.

The present study was designed to determine the hemodynamic changes underlying the hypertension induced by chronic intrarenal infusion of norepinephrine (NE) in conscious rats. NE was infused for a 5-day period intrarenally with osmotic minipumps via a chronic catheter in the right suprarenal artery at rates of 4 and 36 micrograms . kg-1 . hr-1 or intravenously at a rate of 36 micrograms . kg-1 . hr-1. Control rats received a 1 microliter . hr-1 intrarenal infusion of pyrogen-free 0.9% NaCl. In separate experiments, short-term effects were measured continuously during a 22- to 24-hour intrarenal infusion of 4 and 36 micrograms NE . kg-1 . hr-1 or intravenous infusion of 36 micrograms NE . kg-1 . hr-1. Intrarenal infusion of NE produced a more pronounced long-term hypertensive effect than infusion of the same dose intravenously. This hypertension was characterized by a rapid and sustained increase in total peripheral resistance index (TPRI). Despite of the initial renal vasoconstriction, specifically produced during the first 24 hours of intrarenal NE application, cardiac index (CI) in parallel to stroke volume index (SVI) decreased significantly during intrarenal as well as during intravenous NE infusion. Furthermore, no signs of sodium retention were observed. Both rates of intrarenal NE infusion have been shown previously to produce a significant long-term increase in plasma potassium concentration, and the present study indicates that this is presumably the result of decreased urinary potassium output. It is concluded that chronic hypertension produced by intrarenal or intravenous infusion is not volume-dependent. The relatively greater increase in TPRI during intrarenal NE infusion is attributed to vascular wall receptor sensitization by increased plasma potassium levels resulting from effects of intrarenally present NE on tubular cation exchange mechanisms.

Animals↗