PubMed Health⌕ Search

Biomedical subjects

J F Smits

Publications and source records attributed to J F Smits.

At least 109 records · Page 6Linked to original sources
PubMed1987

Adrenergic stimulation of the rat mesenteric vascular bed: a combined micro- and macrocirculatory study.

The sympathetic nervous system is one of the primary factors controlling vascular resistance. Vascular smooth muscle contraction by sympathetic stimulation is mediated primarily by alpha-adrenoceptors. In this study, we investigated the effects of different forms of adrenergic stimulation on simultaneously measured macro- and microcirculatory dynamics in the rat mesenteric vascular bed. Macrocirculatory effects were measured by means of registration of changes in mean arterial pressure (MAP) and blood flow feeding this tissue via a miniaturized Doppler flow probe around the superior mesenteric artery. Microvascular changes were measured at the level of A2 arterioles by means of intravital microscopic registration of arteriolar diameters and red blood cell velocity (RBC vel). Topical or intra-arterial application of noradrenaline caused a dose-dependent decrease in arteriolar diameter and RBC vel at doses that did not cause significant systemic effects. On the other hand, during intravenous application of noradrenaline or other vasopressor substances an increase in MAP and decrease in organ (Doppler) blood flow was not parallelled by a decrease in arteriolar diameter or RBC vel. In contrast, RBC vel increased in a dose-related manner, whereas arteriolar diameter only secondarily decreased to a small degree. Similar results were obtained when the sympathetic nervous system was activated by means of electrical stimulation of the posterior hypothalamus. These data indicate that adrenergic stimulation can elicit different vascular responses. The ultimate microvascular effect depends upon the way of stimulation or route of drug administration.

Animals↗
PubMed1987

Effects of ketanserin on hemodynamics and baroreflex effects in conscious spontaneously hypertensive rats.

Ketanserin is an antihypertensive compound that binds to 5-HT2 receptors as well as to alpha 1-adrenoceptors. The relative importance of the two pharmacological interactions is still unclear. In the present study we compared the central hemodynamic effects of ketanserin with those of the alpha 1-adrenoceptor antagonist prazosin in conscious, unrestrained spontaneously hypertensive rats (SHR). Both drugs rapidly reduced mean arterial pressure (0.1 mg/kg prazosin, -22 +/- 3%; 3 mg/kg ketanserin, -27 +/- 4%) and total peripheral resistance (30 +/- 4 and 26 +/- 4%, respectively). The compounds differed with respect to their effects on heart rate and cardiac output, which increased following prazosin treatment and did not change following ketanserin administration. To investigate involvement of the baroreflex in the latter phenomenon, SHR were challenged with angiotensin II and sodium nitroprusside to increase and decrease blood pressure. Ketanserin did not influence bradycardia following elevation of blood pressure. However, reduction of blood pressure with nitroprusside following ketanserin treatment resulted in extreme vagal bradycardia. This phenomenon was not observed following administration of other antihypertensive agents or serotonin antagonists in SHR. We conclude that this latter interaction with the baroreflex is specific for ketanserin and that it may substantially contribute to its antihypertensive effect. The exact pharmacological mechanism underlying this effect is still under investigation.

Angiotensin II↗
PubMed1987

Adrenoceptors in the kidney: localization and pharmacology.

The kidney plays a key role in the regulation of blood pressure. The sympathetic nervous system can influence many aspects of kidney function in relation to blood pressure control, e.g. renal vascular tone, intrarenal renin release and tubular reabsorption of electrolytes and fluid. The intrarenal distribution of adrenoceptors has now been studied on the basis of modern receptor ligand binding techniques combined with microscopic studies. The preferential localization of each adrenoceptor subtype within the kidney is reviewed. Furthermore, an attempt is made to describe the functional correlation of the presence of different adrenoceptor subtypes. Finally, the possible role of renal adrenoceptor abnormalities in the pathogenesis of hypertension is discussed.

Animals↗
PubMed1987

Characterization of hypertension induced by long-term intrarenal norepinephrine infusion in conscious rats.

This paper reviews some of the data that we have collected over the last years in an animal model in which, to study the role of renal nerves in hypertension, increased efferent sympathetic activity was simulated by a 5-day intrarenal infusion of norepinephrine (NE; 4-36 ug/kg.hr) in rats. This resulted in an exaggerated hypertensive reaction as compared to intravenous infusions of the same amounts. Hypertension was characterized by increased total peripheral resistance and decreased cardiac output. From plasma volume and renal function studies, no evidence for volume-dependent hypertension could be obtained. The most striking difference between intrarenally and intravenously infused rats was a greater increase in plasma NE levels in the former group. This pointed towards a possible activation of afferent renal nerves by intrarenally applied NE. However, neither total nor selective afferent renal denervation prevented hypertension by intrarenal NE. This suggests either that afferent renal nerves do not play a role or, alternatively, blood pressure is controlled differently in intact and denervated rats.

Afferent Pathways↗
PubMed1987

Role of sensory renal nerves in the development of spontaneous hypertension in rats.

In order to study the role of afferent renal nerves in the development of spontaneous hypertension, 3-4 weeks old uninephrectomized spontaneously hypertensive rats were deafferented selectively by a unilateral dorsal rhizotomy. Control rats were sham-operated. Until 10 weeks of age, systolic tail cuff blood pressures were identical in both groups. Although from 12 weeks on systolic blood pressure was slightly (10%) but significantly lower in deafferented rats, mean arterial pressures from an indwelling catheter were identical in deafferented and control rats. We therefore conclude that a selective destruction of afferent renal nerves does not delay or prevent the development of spontaneous hypertension in rats.

Animals↗
PubMed1987

Differential effects of general anesthetics on regional vasoconstrictor responses in the rat.

Although many cardiovascular experiments are performed in the presence of anesthetics, little is known about the depressant effect on regional vascular reactivity. The effect of 2 commonly used anesthetics, pentobarbital (PB) and a chloralose urethane mixture (C-U) on vascular reactivity of different tissues was studied in rats. In order to measure blood flow, rats were equipped with miniaturized Doppler flow probes on the renal artery, the superior mesenteric artery and abdominal aorta. Catheters were implanted for measuring blood pressure and for i.v. injections of differently acting vasopressor substances. Vasoconstriction was induced by i.v. noradrenaline (NA), phenylephrine (P) and angiotensin II (AII), in conscious animals and in anesthetized rats (PB or C-U). The 3 vasopressor substances caused a dose-dependent increase in regional vascular resistances. In anesthetized animals, constrictor responses following P were not affected in any beds. PB diminished the effect of NA and AII in all vascular beds studied, while C-U only depressed renal and splanchnic reactivity. During C-U anesthesia, hindquarter vascular reactivity was not affected. This indicates that anesthetics exert differential regional effects, depending upon the substances studied. This complicates extrapolation of experimental data from one bed to other vascular beds or to conscious animals.

Anesthetics↗
PubMed1986

Beta-adrenoceptors in kidney tubules of spontaneously hypertensive and normotensive rats.

Beta-adrenoceptor binding characteristics were determined in different fractions of rat kidney tubules using a [125Iodo]-(-)-cyanopindolol (ICYP) binding assay. The highest amount of binding sites was found in a fraction containing predominantly distal tubular fragments. In a separate series of experiments the ICYP binding characteristics were compared in whole tubular fractions from spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY) of different ages. The maximum number of binding sites was significantly higher both in young (3 weeks) and adult (14 weeks) SHR when compared to age-matched WKY. These studies showed the presence of beta-adrenoceptor binding sites in rat kidney tubules and support the potential importance of tubular beta-adrenoceptors in the development of spontaneous hypertension and in the mechanism of antihypertensive action of beta-blockers.

Animals↗
PubMed1986

Lack of renal vasodilation during intrarenal infusion of synthetic atriopeptin II in conscious intact SHR.

Synthetic atriopeptin II (APII) was infused directly into the right renal artery of intact conscious SHR at rates of 0.25-1 microgram/kg/min, while simultaneously measuring blood pressure (MAP) and selected regional blood flows. The latter were measured using chronically implanted miniaturized Doppler flowprobes that were placed on the right and left renal artery, superior mesenteric artery and abdominal aorta. The effects of intrarenally (i.r.) infused APII on these vascular beds were compared to the effects of the same amounts of APII given intravenously (i.v.) in the same SHR. I.r. and i.v. infusions caused similar reductions of MAP and all four blood flows. Also effects on calculated resistances were comparable, implying that resistance increased most in the mesentery and least in the two kidneys. The increase in right renal resistance during i.v. infusions of APII was not different from the effect during i.r. infusions. Also, during i.r. infusions into the right kidney, effects on the left and right kidney were not different. Our observations suggest that synthetic APII has no direct effects on the renal vasculature of intact conscious SHR.

Animals↗
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

Local treatment of renal allografts, a promising way to reduce the dosage of immunosuppressive drugs. Comparison of various ways of administering prednisolone.

A method is described for continuous administration of immunosuppressive drugs directly into rat renal allografts. The drug is given via a catheter, introduced into the suprarenal or testicular artery of the transplanted kidney. The cannula is connected to an implantable osmotic minipump that delivers an immunosuppressive drug with continuous flow for 13 days. It is demonstrated that the technique as such has no detrimental or enhancing effects on renal allograft survival. Depending upon the pharmacokinetic properties of the drug administered, this technique allows a more or less selective treatment of renal allograft rejection. The method was used to test the effect of intrarenal administration of prednisolone on renal allograft survival. Intrarenal administration of this drug appeared to be superior to any other way of administration tested. A low dose of 4 mg/kg body weight per day given by continuous intrarenal infusion results in significant prolongation of graft survival, whereas continuous systemic administration of this dose is not effective. To induce prolongation of graft survival by i.p. administration the prednisolone dose had at least to be doubled. The results prove that during graft rejection local events within the graft are vulnerable to prednisolone. It is concluded that local treatment of allograft rejection is possible and that this approach represents a potentially important way to manipulate the immune response.

Animals↗
PubMed1986

The effect of pentobarbitone anaesthesia and hypothermia on the hepatic clearance of indocyanine green and S(-)-acenocoumarol in the rat.

The effect of pentobarbitone anaesthesia and the effect of hypothermia associated with the anaesthesia on the blood clearance of indocyanine green (ICG) and of S(-)-acenocoumarol (AC) was investigated in male Wistar rats using the constant rate infusion technique. During anaesthesia, body temperature was regulated by heat supply. At normothermia (rectal temperature of 37.5 degrees C), pentobarbitone anaesthesia decreased ICG clearance from 8.0 +/- 1.7 ml min-1 (mean +/- s.e.m., n = 3) in the conscious state to 4.3 +/- 0.6 ml min-1 and AC clearance from 4.9 +/- 0.4 ml min-1 to 3.4 +/- 0.3 ml min-1. Hypothermia further reduced the clearances of the compounds to 0.9 +/- 0.1 and 2.5 +/- 0.2 ml min-1 for ICG and AC, respectively. The effect of hypothermia was reversible. The results show that pharmacokinetic constants obtained in the anaesthetized animal may differ greatly from those in the conscious one. If pharmacokinetic experiments are performed in the anaesthetized animal, body temperature should be controlled and a slight hyperthermia is most favourable. Our pharmacokinetic data on ICG seriously question the use of this drug to estimate liver blood flow in the rat.

Acenocoumarol↗
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↗
PubMed1986

Regional hemodynamic effects of the beta-adrenoceptor blockers tertatolol and propranolol in conscious spontaneously hypertensive rats.

The effects of the beta-adrenoceptor blocking drugs propranolol and tertatolol on regional hemodynamics were studied in conscious spontaneously hypertensive rats (SHR). Regional blood flows were measured using a 20 MHz directional pulsed Doppler system with miniaturized Doppler probes on the left renal artery, the superior mesenteric artery and the abdominal aorta. This allowed the determination of changes in resistances in the renal (RR), mesenteric (MR) and hindquarter (HQR) vascular beds. Tertatolol and propranolol caused an immediate fall in heart rate. Mean arterial pressure (MAP) increased during the first 15-30 min following injection of the beta-blockers. Thereafter it gradually fell below control values to reach significant decreases in MAP 3-4 hr following injection. Fifteen to thirty min after propranolol, vascular resistances increased in all 3 vascular beds significantly. Resistances returned to control values over the next 3-4 hr. Following tertatolol, HQR increased significantly during the first 15-30 min. MR and RR did not increase significantly whereas a significant fall in RR was observed after 3-4 hr. These data indicate different regional hemodynamic effects for tertatolol and propranolol in the conscious SHR. Tertatolol does not cause the renal and mesenteric vaso-constriction observed following propranolol.

Adrenergic beta-Antagonists↗
PubMed1985

Systemic and regional hemodynamic actions of calcium entry blockers in conscious spontaneously hypertensive rats.

In the present study we investigated systemic and regional hemodynamic effects of the calcium entry blockers nifedipine, verapamil and PY 108-068 in conscious SHR. For systemic hemodynamic studies the animals were instrumented with an electromagnetic flowprobe on the ascending aorta, whereas for regional hemodynamic studies miniaturized Doppler flowprobes were implanted on the superior mesenteric and left renal artery and on the abdominal aorta. All three drugs caused a dose-dependent fall in mean arterial pressure and total peripheral resistance. Nifedipine and PY 108-068 increased cardiac output and heart rate, whereas verapamil only did so at high doses. Administration of each calcium entry blocker caused a dose-dependent fall in skeletal muscle vascular resistance, with renal and mesenteric resistance remaining virtually unchanged. A similar effect was observed after the administration of nifedipine to normotensive WKY rats. Surgical elimination of sino-aortic baroreflexes caused a 10 fold increase in antihypertensive potency of the three drugs in SHR. Moreover, dilatation in these animals was uniform in all beds studied. The results indicate that the three calcium entry blockers used are essentially non-selective vasodilators but that baroreflex mechanisms prevent vasodilatation in the renal and mesenteric beds in intact animals.

Animals↗
PubMed1985

Selective efferent chemical sympathectomy of rat kidneys.

Surgical denervation of kidneys results in interruption of both afferent and efferent renal nerves. We attempted selective efferent renal denervation in rats by slow infusions of 6-hydroxydopamine (6-OHDA) into the right renal artery. Integrity of efferent renal nerves was assessed by chemical and physiological methods and by measuring responses of mean arterial blood pressure (MAP) and heart rate (HR) to intrarenal (ir) infusion of bradykinin in conscious rats. Results were compared with those in surgically denervated and ir saline-infused rats. Surgical denervation of left kidney reduced renal norepinephrine (NE) to 58 and 14% of control levels at 1 and 7 days, respectively, after surgery. Increase in left renal resistance during posterior hypothalamus (PH) stimulation was only 70 +/- 28% (n = 5) compared with 289 +/- 69% (n = 6) in control animals. Response in opposite kidney was unchanged. Although 0.1 mg 6-OHDA ir caused considerable reduction of NE levels in both kidneys, responses to PH stimulation were unchanged. 6-OHDA (1 mg) reduced NE levels in infused and control kidney and atria. Functional evidence for denervation was only obtained in the kidney infused with 6-OHDA. Responses of MAP and HR to ir bradykinin were unchanged 7 days after 1 mg 6-OHDA. The data suggest that ir 6-OHDA results in functional efferent sympathectomy without affecting afferent renal nerves.

Animals↗
PubMed1985

Failure of atriopeptin II to cause arterial vasodilation in the conscious rat.

The cardiovascular actions of the synthetic natriuretic peptide, atriopeptin II, were examined in conscious unrestrained spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. The animals were chronically instrumented with miniaturized pulsed Doppler flow probes to allow measurement of regional blood flow, or with an electromagnetic flow probe on the ascending aorta to facilitate the measurement of cardiac output in the conscious rat. Intravenous infusion of increasing doses of atriopeptin II (0.25-4 micrograms/kg per min) caused a dose-dependent fall in mean arterial pressure in the hypertensive and normotensive rats. Blood flow in the renal, mesenteric, and hindquarters vascular beds was markedly decreased during the infusion of atriopeptin II, and regional vascular resistance was significantly increased in both groups of rats. Heart rate was significantly elevated (47 +/- 14 beats/min) in the spontaneously hypertensive rats during atriopeptin II infusion, but no change in heart rate was observed in the Wistar rats. In the hypertensive rats, atriopeptin II caused a marked dose-dependent decrease in cardiac output (maximal decrease = -39 +/- 4%) and stroke volume (maximal decrease = -48 +/- 4%). Central venous pressure and left atrial pressure were also significantly reduced during atriopeptin II infusion. Total peripheral resistance was increased over the infusion protocol by 26 +/- 3%. These data suggest that atriopeptin II infusion markedly attenuated cardiac output in the conscious spontaneously hypertensive rats. Total and regional vascular resistances were increased, possibly through reflex compensatory mechanisms, to maintain arterial pressure in the face of decreased cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗