Biomedical subjects

F Ferrante

Publications and source records attributed to F Ferrante.

At least 37 records · Page 2Linked to original sources

PubMed1995

Protective effect of nicardipine treatment on cerebrovascular microanatomical changes in spontaneously hypertensive rats.

1. The effect of long-term treatment with the dihydropyridine Ca2+ antagonist, nicardipine, on the morphology of different sized pial arteries was assessed in spontaneously hypertensive rats (SHR) using histological techniques associated with image analysis. 2. In control 20 week old SHR blood pressure values, the thickness of the tunica media, the media-to-lumen ratio and connective tissue content were significantly increased in comparison with reference normotensive Wistar-Kyoto (WKY) rats. 3. Treatment for 8 weeks with a daily dose of 3 mg/kg of nicardipine decreased blood pressure values in SHR and significantly reduced the area occupied by the tunica media and the media-to-lumen ratio. This effect was observed primarily in small sized pial arteries and to a lesser extent in medium sized pial arteries. Nicardipine administration was without effect on connective tissue content in the wall of cerebral arteries. 4. These results indicate that treatment with nicardipine reduces blood pressure elevation in SHR and exerts a protective effect on arteries controlling cerebrovascular resistance. The activity of the compound primarily on small sized pial arteries may protect the brain from generalized vasodilation which could cause cerebral hypoperfusion.

Animals↗

PubMed1995

Influence of long-term treatment with the dihydropyridine-type calcium antagonist nicardipine on renal microanatomical changes in spontaneously hypertensive rats.

1. The influence of hypertension and treatment with the dihydropyridine-type Ca2+ antagonist, nicardipine, on the structure of the kidney was assessed in spontaneously hypertensive rats (SHR) of 12 weeks of age. Treatment went for 8 weeks with a daily oral dose of 1 mg/kg of nicardipine. 2. Control SHR exhibited hypertension and microanatomical vascular and glomerular changes. Vascular changes consisted of a thickening of the tunica media and decreased luminal area of medium- and small-sized intrarenal artery branches. Glomerular changes included glomerulosclerosis and atrophy of varying degrees. 3. Administration of nicardipine significantly reduced blood pressure. The drug also decreased the thickening of tunica media and luminal narrowing of renal artery branches as well as the degree of glomerular injury in SHR. 4. These data indicate that nicardipine treatment is able to control elevated blood pressure in SHR, and to counter hypertension-dependent microanatomical impairment of the kidney. This suggests that the compound exerts a protective effect on hypertensive kidney.

Animals↗

PubMed1995

Pharmacological characterisation and autoradiographic localisation of dopamine receptor subtypes in the cardiovascular system and in the kidney.

Combined radioligand binding and light microscope autoradiography techniques were used for investigating the pharmacological profile and the microanatomical localisation of dopamine receptor subtypes in the cardiovascular system and in the kidney. In superior mesenteric and renal arteries the predominant dopamine D1-like receptor belongs to the D5 (or D1b) subtype. This site is located within smooth muscle of the tunica media. The same receptor subtype predominates in the kidney, where it has a vascular and tubular localisation. The dopamine D2-like receptor subtype expressed by systemic arteries belongs to the D2 receptor subtype. It has a prejunctional and endothelial localisation. In the kidney the predominating dopamine D2-like receptor belongs to the dopamine D3 subtype. Atria but not ventricles express dopamine D2-like receptors belonging to the D4 receptor subtype. The above results suggest that in spite of the emerging complexity of the dopamine receptor profile demonstrated by molecular biology techniques, radioligand binding and autoradiographic techniques, if performed with appropriate radioligands and/or in the presence of compounds active on specific receptor subtypes, may represent a useful tool for better understanding the biological significance of peripheral dopamine receptors.

Animals↗

PubMed1995

Localization of calcium channels of the L-type in human epicardial arteries: a light microscope autoradiographic study.

The anatomical localization of Ca2+ channels of the L-type was analyzed in sections of the human right and anterior interventricular coronary arteries by using in vitro light microscope autoradiography associated with radioligand binding techniques. [3H]Nicardipine was utilised as a ligand. Binding of the radioligand to sections of the two coronary arteries was time-, temperature- and concentration-dependent. Analysis of binding isotherms revealed a dissociation constant value of about 0.5 nM in the two arteries and maximum binding capacities of 139 +/- 6.4 fmol/mg tissue for the right coronary artery and of 173 +/- 9.5 for the anterior interventricular branch. The pharmacological profile of [3H]nicardipine binding to sections of human coronary arteries was consistent with the labelling of Ca2+ channels of the L-type. Dihydropyridine derivatives were the most powerful competitors of [3H]nicardipine binding, whereas phenylalkylamines, benzothiazepine or non-selective channel modulators were weak competitors or ineffective. Light microscope autoradiography revealed the highest density of [3H]nicardipine binding sites in the tunica media of the coronary arteries. In this layer Ca2+ channels of the L-type are located within smooth muscle cells. A lower accumulation of the radioligand occurred in the tunica adventitia, whereas no specific binding was found in the tunica intima. Study of the localization of Ca2+ channels in sections of human coronary arteries may contribute to a better understanding of the mechanism of the marked coronary dilatory activity elicited by Ca2+ antagonists demonstrable in both in vitro preparations and in vivo.

Adolescent↗

PubMed1994

Dopamine D1 receptors are involved in the ACTH-induced reversal of hemorrhagic shock.

In an experimental model of volume-controlled hemorrhagic shock causing the death of all rats within 30 min, the intravenous (i.v.) bolus injection of the adrenocorticotropic hormone fragment 1-24 (ACTH-(1-24)) (160 micrograms/kg) induced a prompt and sustained improvement of cardiovascular and respiratory function, with 100% survival 2 h after treatment. Pretreatment with either haloperidol, 300 micrograms/kg i.v. (antagonist at dopamine D1 and D2 receptors), or (R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3- benzazepin-7-ol hemimaleate (SCH 23390), 50 micrograms/kg intraperitoneally (selective antagonist at dopamine D1 receptors), significantly inhibited the effect of ACTH-(1-24). A complete inhibition was produced by intracerebroventricular pretreatment with SCH 23390 (0.1 micrograms/rat). On the other hand, both i.v. and i.c.v. pretreatment with l-sulpiride (selective antagonist at dopamine D2 receptors) (25 mg/kg and 80 micrograms/rat, respectively) had only minor effects. These data suggest that the mechanism of the ACTH-induced reversal of hemorrhagic shock involves the activation of dopamine D1 receptors in the brain.

Analysis of Variance↗

PubMed1994

Influence of treatment with L-deprenyl on the structure of the cerebellar cortex of aged rats.

Treatment with L-deprenyl increases mean and maximum life span in the rat and reverses memory and learning deficits associated with old age. Since only sparse information is available concerning the influence of L-deprenyl administration on the aging brain microanatomy, we have investigated the effect of long-term treatment with L-deprenyl on the structure of the cerebellar cortex in the aged rat. The cerebellar cortex was used since it represents a useful model for assessing age-related changes in nervous system anatomy and function. Male Sprague-Dawley rats were treated from the 19th to the 24th month of age with a daily oral dose of 1.25 mg/kg or 5 mg/kg L-deprenyl. Age-matched rats were left untreated and used as a control group. Eleven-month-old untreated rats were used as an adult reference group. The density of Purkinje and granule neuron profiles as well as the intensity of Nissl's staining within the cytoplasm of Purkinje neurons were reduced in 24-month in comparison with 11-month rats. Moreover, an increased accumulation of lipofuscin was noticeable in the cytoplasm of Purkinje neurons of old rats as well as an increase in MAO-B activity in the molecular layer of the cerebellar cortex. The two doses of L-deprenyl increased the density of both Purkinje and granule neuron profiles and the intensity of Nissl's staining in the cytoplasm of Purkinje neurons and reduced lipofuscin deposition within Purkinje neurons. The lower dose of L-deprenyl caused only a slight decrease in MAO-B activity, whereas the 5-mg/kg/day dose remarkably reduced it. These results suggest that long-term treatment with L-deprenyl counters the expression of some age-related microanatomical changes in the rat cerebellar cortex. The possible independence of the effects of the compound on age-related microanatomical changes of the cerebellar cortex and on MAO-B inhibitory activity is discussed.

Aging↗

PubMed1994

Long term choline alfoscerate treatment counters age-dependent microanatomical changes in rat brain.

1. The density of nerve cells and of silver-gold impregnated fibres were evaluated in the hippocampus and in the cerebellar cortex in adult (12-month-old) and old (24-month-old) Sprague-Dawley rats. 2. The effects of long-term choline alfoscerate (GFC) treatment (100 mg/Kg/day for 6 months) on the above parameters were investigated in old rats. 3. The number of nerve cell profiles and the area occupied by silver-gold impregnated fibres were decreased both in the hippocampus and in the cerebellar cortex in old in comparison with adult rats. 4. GFC treatment countered the age-dependent reduction of nerve cells and silver-gold impregnated fibres. The hippocampus was more sensitive than the cerebellar cortex to the activity of GFC. 5. These results suggest that GFC treatment is effective in slowing down the expression of structural changes occurring in aging brain.

Aging↗

PubMed1994

Microanatomical changes in the frontal cortex of aged rats: effect of L-deprenyl treatment.

The present study was designed to assess whether treatment with L-deprenyl has any effect on the age-related microanatomical changes in the rat frontal cortex. Male Sprague-Dawley rats of 19 months of age were treated until the 24th month with an oral daily dose of 1.25 mg/kg or of 5 mg/kg of L-deprenyl. Eleven-month-old untreated rats were used as an adult reference group. The density of nerve cell profiles and of glial fibrillary acidic protein-(GFAP) immunoreactive astroglial profiles, lipofuscin accumulation within the cytoplasm of pyramidal neurons, and MAO-B reactivity were assessed. A decreased density of nerve cell profiles and an increased density of astroglial profiles as well as augmented lipofuscin deposition and MAO-B reactivity were observed in the frontal cortex of rats of 24 months in comparison with 12-month-old animals. In the frontal cortex of rats treated with 5 mg/kg/day L-deprenyl, which is a dose inhibiting MAO-B activity, the density of nerve cell and GFAP-immunoreactive astrocyte profiles is increased and decreased respectively in comparison with age-matched untreated subjects. Lipofuscin deposition is reduced. The lower dose of L-deprenyl (1.25 mg/kg/day) which did not affect MAO-B activity, decreased lipofuscin deposition but was without effect on the density of nerve cell or GFAP-immunoreactive astrocyte profiles. The above findings suggest that treatment with L-deprenyl is able to counter some microanatomical changes occurring in the frontal cortex of aged rats. Some of these effects are probably not related to the inhibitory MAO-B activity of the compound.

Aging↗

PubMed1994

Interactions between endothelin and the dihydropyridine-type calcium antagonist nicardipine in the human renal artery: a radioligand and autoradiographic study.

The interactions between dihydropyridine Ca2+ channels and endothelin were analysed using combined radioligand binding and autoradiographic techniques. Endothelin is a potent constrictor peptide of arterial smooth muscle. Endothelin-induced vasoconstriction is attenuated by dihydropyridine-type Ca2+ antagonists such as nicardipine. However, the molecular mechanisms of this effect are not yet understood. Sections of the human renal artery bound [3H]-nicardipine in a manner consistent with the labelling of dihydropyridine-type Ca2+ channels. The highest density of [3H]-nicardipine binding sites occurred within the tunica media of the renal artery, probably over smooth muscle. A lower density of [3H]-nicardipine binding sites was noticeable in the tunica adventitia, whereas no specific binding occurred in the tunica intima. Endothelin-1, from a concentration of 1 pM l-1, reduced [3H]-nicardipine binding as a function of concentration. A 10 nM endothelin concentration reduced [3H]-nicardipine binding by about 85%. The isoform, endothelin-3, had little effect on [3H]-nicardipine binding. The above findings suggest the occurrence of an interaction, probably at the receptor level, between [3H]-nicardipine binding and endothelin-1. This interaction probably accounts for the attenuation of endothelin-1-elicited vasoconstriction induced by nicardipine.

Aged↗

PubMed1994

Protective effect of nicardipine treatment on renal microanatomical changes in spontaneously hypertensive rats.

The effects of nicardipine administration on kidney morphology were studied in spontaneously hypertensive rats (SHR). Male 12-week-old SHR received an oral dose of 1 mg/Kg/day of nicardipine or vehicle for 8 weeks Age-matched Wistar-Kyoto rats were used as normotensive reference animals. At 20 weeks, the non treated SHR exhibited hypertension, albuminuria, decreased urinary sodium excretion and renal microanatomical changes. These changes were characterized by vascular alterations consisting in hypertrophy of the tunica media accompanied by a decrease of luminal surface. Glomerular changes consisting primarily in signs of glomerulosclerosis of varying degrees were noticeable in the kidneys of SHR. Treatment with nicardipine significantly reduced blood pressure and albuminuria and increased urinary sodium excretion. Moreover, hypertrophy of the tunica media and the luminal surface were decreased and increased respectively in nicardipine-treated SHR. The above results suggest that treatment with nicardipine reduces blood pressure in SHR and counteracts hypertension-dependent changes in the morphology of the kidney. The protective effect of the drug on hypertensive changes of renal microanatomy probably have functional relevance given of the influence of nicardipine treatment on albuminuria and urinary sodium excretion in SHR.

Albuminuria↗

PubMed1994

Influence of isradipine treatment on left ventricular and coronary vascular hypertrophy in spontaneously hypertensive rats.

The purpose of this study was to ascertain if Isradipine treatment in spontaneously hypertensive rats (SHR) decreased hypertension-dependent left ventricular and coronary vascular hypertrophy. Twelve week male SHR were used in this study; one group of SHR was treated with Isradipine while the control group of SHR was left untreated. Age-matched normotensive Wistar-Kyoto rats (WKY) were utilized as a reference group. After 12 weeks of treatment rats were sacrificed. The hearts were removed and morphometric analysis was performed on the left ventricles. Isradipine treatment reduced systolic blood pressure in SHR. The heart/body weight ratio significantly increased in SHR and in Isradipine-treated SHR in comparison with WKY rats. Isradipine treatment decreased the left ventricular muscle fibre diameter and decreased the amount of focal necrosis in SHR. Different sized coronary arteries were also examined using a light microscope and an image analyzer. We found that the area occupied by the medial layer and the media-to-lumen ratio were significantly increased in comparison with WKY rats. In Isradipine-treated SHR the area of the medial layer and the media-to-lumen ratio in small and medium sized but not in large sized coronary arteries were significantly reduced in comparison with untreated SHR. The above results suggest that long term Isradipine treatment is not only able to reduce high blood pressure in SHR but is also able to counter the development of certain morphological changes often seen in the hypertensive heart and coronary arteries.

Animals↗

PubMed1994

Influence of treatment with the calcium channel blocker darodipine (PY 108-068) on the morphology of pial and coronary arteries in spontaneously hypertensive rats.

The present study was designed to assess the influence of treatment with the calcium channel blocker darodipine (PY 108-068) on the morphology of pial and coronary arteries in spontaneously hypertensive rats (SHR). Twelve week male SHR were used in this study. One group was treated with a daily dose of 5 mg/Kg of darodipine, while the control group of SHR was treated with placebo. Age-matched normotensive Wistar Kyoto (WKY) rats were used as a reference group. After 12 weeks of treatment the rats were sacrificed. The brains and the hearts were removed, embedded in resin, cut and used for light microscope analysis. Darodipine treatment reduced blood pressure in SHR. Morphometric analysis of different sized pial and coronary arteries revealed decreased arterial lumen in SHR in comparison with WKY rats. The area occupied by the tunica media and the media-to-lumen ratio were increased in SHR in comparison with WKY rats. In darodipine-treated rats the area occupied by the arterial lumen was increased in comparison with control SHR, whereas the area occupied by the tunica media and the media-to-lumen ratio were decreased. Pial arteries were more sensitive than coronary arteries to darodipine treatment. Medium and small sized pial and coronary arteries were most sensitive to darodipine treatment. Large-sized coronary artery branches were unaffected by pharmacological treatment. The above results suggest that treatment of SHR with darodipine is able to reduce high blood pressure and to counter the development of structural changes of pial and coronary arteries noticeable in SHR. The higher sensitivity of the cerebral vasculature to darodipine treatment is discussed.

Animals↗

PubMed1994

Quantitative image analysis study of the cerebral vasodilatory activity of nicardipine in spontaneously hypertensive rats.

The effect of the Ca2+ channel blocker nicardipine on the circle of Willis and the different sized pial arteries was assessed in 20-week-old spontaneously hypertensive rats (SHR) using quantitative image analysis techniques. Normotensive Wistar Kyoto (WKY) rats were also used as a normotensive reference group. In SHR a significant increase of systolic blood pressure (SBP) is noticeable in comparison with WKY rats. The media-to-lumen ratio was increased in the circle of Willis arteries, large sized (diameter > than 150 microns), medium sized (diameter between 150 and 50 microns) and small sized (diameter < than 50 microns), pial artery branches. An increase in the thickness of the tunica media and a luminal narrowing was also seen in medium and small sized pial arteries of SHR in comparison with WKY rats. Treatment with an oral dose of 10 mg/Kg of nicardipine 3 h before the sacrifice significantly reduced SBP in SHR. The drug was without effect on circle of Willis and on large sized pial arteries. Moreover, treatment with nicardipine reduced the thickness of the tunica media, the media-to-lumen ratio and increased the luminal area in medium and small sized pial artery branches. These findings show that treatment of SHR with nicardipine significantly reduces SBP and causes a moderate vasodilatation of arteries regulating cerebrovascular resistance. This property may be useful in avoiding generalized or exaggerated cerebrovascular dilatation which could be accompanied by impaired brain perfusion in hypertension.

Animals↗

PubMed1994

Effect of long term isradipine treatment on the morphology of the endothelium in the aorta of spontaneously hypertensive rats.

The influence of hypertension and of treatment with the dihydropyridine calcium channel blocker isradipine on the morphology of the thoracic aorta and of the aortic tunica intima were studied. Three experimental groups of male spontaneously hypertensive rats (SHR) of 10 weeks of age were used. Two groups were treated with a daily oral dose of 0.01 mg/kg or of 0.1 mg/Kg of isradipine respectively. A third group of SHR was left untreated and served as control. Age-matched normotensive Wistar-Kyoto (WKY) rats were used as a reference group. Animals were allowed to survive for 12 weeks and were killed at 22 weeks of age. Systolic pressure values which did not change in WKY rats, significantly increased in SHR as a function of age. The dose of 0.1 mg/Kg/day isradipine reduced systolic pressure to normotensive values after the first week of treatment, whereas the lower one was ineffective. The area of the wall, the area of the tunica media and the wall-to-lumen ratio of the aorta significantly increased in SHR and decreased either with the antihypertensive and non-antihypertensive doses of isradipine. Transmission and scanning electron microscope analysis of the tunica intima revealed hypertrophy of the endothelial cells with an increase in sub endothelial space in SHR. An improvement of the endothelial morphology and a decrease in sub endothelial space was noticeable in isradipine-treated SHR. Although the hypotensive dose of the compound was the most effective, the non-hypotensive dose was active was well. The above results suggest that isradipine treatment may counter structural changes of the aorta of SHR and has a protective action on the hypertension-dependent modifications of the endothelium. The endothelial effects are probably dependent only in part by the hypotensive activity of the compound.

Animals↗

PubMed1994

Influence of isradipine treatment on the morphology of the aorta in spontaneously hypertensive rats.

OBJECTIVE: To investigate the influence of hypertension and of treatment with the vasodilator hydralazine or with the dihydropyridine calcium antagonist isradipine on the morphology of the thoracic aorta in spontaneously hypertensive rats (SHR). DESIGN: The systolic blood pressure (SBP), body weight and morphology of the thoracic aorta were evaluated. The ultrastructure of the smooth muscle component of the aorta and of the tunica intima were analysed by transmission and scanning electron microscopy. METHODS: The SHR were divided into three groups: a control group, which was left untreated, and two treatment groups, one with 1 mg/kg per day hydralazine and the other with 0.1 mg/kg per day isradipine. Three age-matched groups of Wistar-Kyoto (WKY) rats were included in the study: one group was left untreated and was used as a normotensive reference group, the other two groups were treated with 1 mg/kg per day hydralazine or with 0.1 mg/kg per day isradipine. RESULTS: The SBP did not change in the WKY rats treated with hydralazine, with isradipine or untreated, but was significantly increased in the SHR as a function of age. Both hydralazine and isradipine significantly reduced the SBP in the SHR after the second week of treatment. Light microscopy analysis of the thoracic aorta revealed thickening of the wall of the tunica media as well as an increase in the wall: lumen ratio in the SHR. Treatment with hydralazine had no effect on the morphometric parameters evaluated, whereas isradipine administration significantly reduced the thickening of both the wall and the tunica media of the aorta, and reduced the wall: lumen ratio. No significant modifications in the structure of the thoracic aorta were noticed in the hydralazine- or isradipine-treated WKY rats compared with untreated WKY rats. Transmission and scanning electron microscopy analysis demonstrated in control SHR hypertrophy of smooth muscle cells of the tunica media, an increased size and impairment of the internal elastic lamina, and a widening of the subendothelial space. Hypertrophy of the endothelium was also noticeable in the SHR. Treatment with isradipine reduced the hypertrophy of smooth muscle cells of the tunica media and the structural impairment of the tunica intima. No effect of isradipine treatment on the morphology of the aorta was noticed in the WKY rats. CONCLUSION: The present results show that the effect of isradipine was different from that of hydralazine. Both compounds lowered the SBP, but only isradipine countered the structural changes of the aorta in the SHR. The effect of isradipine administration is particularly pronounced on the hypertension-dependent changes of endothelium. This suggests that isradipine may have a protective effect on the endothelium.

Animals↗

PubMed1993

Autoradiographic localization of [3H]nicardipine binding sites in the human renal artery.

In the present study the pharmacological profile and the anatomical distribution of dihydropyridine-type Ca2+ channels were analyzed in sections of the human renal artery by the use of combined radioligand binding and autoradiographic techniques with [3H]nicardipine as a ligand. The binding of [3H]nicardipine to sections of renal artery was time-, temperature- and concentration-dependent belonging, at least in the range of radioligand concentrations used, to a single class of high-affinity binding sites. The dissociation constant (KD) value was 0.3 nM and the maximum density of binding sites (Bmax) was 248 +/- 16 fmol/mg tissue. The pharmacological profile of [3H]nicardipine binding to sections of human renal artery was consistent with the labeling of dihydropyridine-type Ca2+ channels. In fact, dihydropyridine derivatives were the most powerful competitors of [3H]nicardipine binding, whereas phenylalkilamine, benzothiazepine or non-selective channel modulators were weak or ineffective competitors. Light microscope autoradiography revealed the highest density of [3H]nicardipine binding sites in the tunica media of the renal artery, probably within smooth muscle cells. A smaller accumulation of the radioligand occurred in the tunica adventitia, whereas the tunica intima did not show specific binding. These results indicate that light microscope autoradiography techniques associated with radioligand binding may represent a useful tool for analyzing the localization of receptors or targets of drug action within the arterial wall.

Aged↗

PubMed1993

Structural changes in the endothelium of the femoral artery of spontaneously hypertensive rats: sensitivity to isradipine treatment.

OBJECTIVE: The present study was designed to investigate the influence of hypertension and of long-term treatment with the dihydropyridine calcium antagonist isradipine on the morphology of the femoral artery in spontaneously hypertensive rats (SHR). DESIGN: Systolic blood pressure (SBP), body weight and morphology of the femoral artery were evaluated, and the ultrastructure of the endothelium was analysed by transmission and scanning electron microscopy. METHODS: SHR were divided into three groups, a control group which was left untreated and two isradipine treatment groups, one at 0.01 mg/kg per day and the other at 0.1 mg/kg per day. Two age-matched groups of Wistar-Kyoto (WKY) rats were included in the study; one group was left untreated and was used as a normotensive reference group and the other was treated with isradipine at 0.1 mg/kg per day. The study lasted 12 weeks. RESULTS: SBP did not change in the WKY rats, whether treated with isradipine or not, but was significantly increased in SHR as a function of age. The lower dose of isradipine did not alter SBP in the SHR, but the higher dose brought SBP values into the normal range after the first week of treatment. Light microscopy of sections of the femoral artery did not reveal any structural differences in the five rat groups examined. Both transmission and scanning electron microscopy showed endothelial alterations in the SHR, together with thickening of the internal elastic lamina. Treatment with isradipine significantly improved the morphology of the endothelium in SHR. The higher dose was more effective, but the lower dose partly countered the hypertension-dependent changes in the morphology of the endothelium. No significant modifications to the structure of the endothelium were noticed in isradipine-treated WKY rats compared with untreated WKY rats. CONCLUSIONS: The results show that structural changes occur in the endothelium of the femoral artery of SHR and that isradipine treatment has a protective effect. This protective effect is probably only partly dependent on the antihypertensive properties of the compound.

Animals↗

PubMed1993

Endothelin-1 displaces [3H]nicardipine binding in sections of human renal artery.

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, the actions of which are mediated through interaction with specific ET receptors. Functional evidence has shown that the constrictor effect of ET may require extracellular Ca2+. Ca2+ antagonists of the dihydropyridine family attenuate the vasoconstriction caused by ET. However, the basis of the interactions between ET and dihydropyridine agents are not well understood. Our study was designed to assess whether different concentrations of ET-1 or ET-3 have any effect on [3H]nicardipine binding to sections of human renal artery. [3H]Nicardipine was specifically bound to sections of the human renal artery. Binding sites, which were located primarily over smooth muscle of the tunica media, showed the pharmacologic profile typical of a dihydropyridine Ca2+ channel. Increasing concentrations of ET-1, but not of ET-3, competed dose-dependently with [3H]nicardipine binding. A 1-nM concentration of ET-1 lessened specific [3H]nicardipine binding by approximately 80%. These results suggest the occurrence of an interaction in the human renal artery between dihydropyridine Ca2+ channels and ET-1. This interaction probably accounts for the inhibition of the ET-1-mediated vasoconstriction elicited by nicardipine.

Adult↗