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S Salomone

Publications and source records attributed to S Salomone.

At least 19 recordsLinked to original sources
PubMed2004

Cistus incanus and Cistus monspeliensis inhibit the contractile response in isolated rat smooth muscle.

The lyophilized aqueous extracts from Cistus incanus L. (CI) and Cistus monspeliensis L. (CM) collected in Sicily were studied in order to evaluate their myorelaxant activity by using isolated smooth muscle of rat ileum and rat aorta. Both CI and CM extracts concentration-dependently inhibited the contractile response to acetylcholine (ACh), phenylephrine (PE) and to 100 mM KCl. The concentration-contraction curves to ACh in ileum and to PE in aorta, were displaced to the right by Cistus extracts in a non-competitive manner, with a depression of the maximum contractile response. The EC50 (microg/ml) of CM and CI were: ileum/KCl, CM 457+/-99, CI 681+/-80; ileum/ACh 100 microM, CM 297+/-66, CI 335+/-41; aorta/KCl, CM 360+/-21, CI 843+/-36; and aorta/PE 10 microM, CM 287+/-33, CI 451+/-58. The two extracts resulted almost equi-active in ileum, whereas CM was more active than CI in aorta. These data indicate that Cistus extracts act as spasmolytic on intestinal and vascular smooth muscle. The antagonism they exert on ACh-, PE- and KCl-evoked contractions seems to be functional, because it is not specifically directed toward any particular receptor; furthermore, a calcium-antagonist activity seems unlikely, since the extracts are capable of completely block the contractile response to agonists.

Acetylcholine↗
PubMed2004

Effects of chronic sumatriptan and zolmitriptan treatment on 5-HT receptor expression and function in rats.

Triptans are commonly used anti-migraine drugs and show agonist action mainly at serotonin 5-HT(1B/1D/1F) receptors. It is not known whether frequent or long-term treatment with these drugs would alter 5-HT receptor function. We investigated the effects of protracted (14-18 days) sumatriptan and zolmitriptan treatment in rats on 5-HT(1) receptor mRNA expression and function in tissues related to migraine pathophysiology. RT-PCR analysis revealed that 5-HT(1B/1D/1F) receptor mRNA was reduced in the trigeminal ganglion after treatment with either triptan (reduction by: sumatriptan 39% and zolmitriptan 61% for 5-HT(1B); 60%vs 41% for 5-HT(1D); 32%vs 68% for 5-HT(1F)). Sumatriptan attenuated 5-HT(1D) receptor mRNA by 49% in the basilar artery, whereas zolmitriptan reduced 5-HT(1B) mRNA in this tissue by 70%. No change in 5-HT(1) receptor mRNA expression was observed in coronary artery and dura mater. Chronic triptan treatment had no effect in two functional assays [sumatriptan mediated inhibition (50 mg/kg, i.p.) of electrically induced plasma protein extravasation in dura mater and 5-nonyloxytryptamine-stimulated [(35)S]guanosine-5'-O-(3-thio)triphosphate binding in substantia nigra]. Furthermore, vasoconstriction to 5-HT in isolated basilar artery was not affected by chronic triptan treatment, while it was slightly reduced in coronary artery. We conclude that, although our treatment protocol altered mRNA receptor expression in several tissues relevant to migraine pathophysiology, it did not attenuate 5-HT(1) receptor-dependent functions in rats.

Animals↗
PubMed2004

Modulation of cerebral vascular tone by activated glia: involvement of nitric oxide.

The ability of activated glia to affect cerebral vascular tone has been evaluated using an in vitro experimental system in which basilar arteries were incubated with glial cultures activated by treatment with lipopolysaccharide (LPS). Vascular tone was measured with an isometric myograph. Contraction in response to high KCl and serotonin was reduced in arteries co-incubated for 24 h with LPS-activated glia, whereas the response to acetylcholine was not modified. The reduced contraction was prevented when the nitric oxide synthase (NOS) inhibitor L-N-nitro-arginine (L-NNA) was added throughout the whole incubation time (activation of glial cells with LPS + co-incubation of glial cells with cerebral arteries). Under these conditions, nitrite levels were drastically reduced. A reduced contraction to KCl was also observed after treatment of the cerebral vessel with sodium nitroprusside. In contrast, L-NNA added to the vessel did not modify the response to contracting stimuli and the expression of endothelial NOS was not modified in cerebral arteries pre-incubated with activated glia. These results suggest that activated glia, which finds an in vivo correlate in several neuropathological conditions, can contribute to changes of vascular tone by modifying the levels of nitric oxide (NO) to which the vessel is exposed.

Acetylcholine↗
PubMed2001

Lacidipine prevents endothelial dysfunction in salt-loaded stroke-prone hypertensive rats.

Endothelium-dependent vasorelaxation is defective in hypertensive rats, especially in conduit arteries. In the stroke-prone spontaneously hypertensive rat, impaired endothelium-dependent vasorelaxation appears to contribute to the pathogenesis of stroke independent of blood pressure. Because treatment with lacidipine, a long-acting calcium channel blocker, protects against stroke and cardiovascular remodeling in this model, we investigated the effect of this treatment on endothelium-dependent vasorelaxation in the aorta. Stroke-prone rats were exposed to a salt-rich diet (1% NaCl in drinking water) with or without lacidipine (1 mg. kg(-1). d(-1)) for 6 weeks. A high-sodium diet (1) increased systolic blood pressure, aortic weight, and wall thickness and plasma renin activity (P<0.05); (2) markedly reduced nitric oxide (NO)-mediated, endothelium-dependent relaxation of aortic rings to acetylcholine and the sensitivity to the relaxing effect of S-nitroso-N-acetylpenicillamine, an NO donor (P<0.001); and (3) induced an elevation of preproendothelin-1 mRNA levels in aortic tissue (P<0.01) without affecting endothelial NO synthase mRNA levels. Lacidipine treatment prevented the salt-dependent functional and structural alterations of the aorta, including the overexpression of the preproendothelin-1 gene, and increased endothelial NO synthase mRNA levels in aortic tissue (P<0.01). In conclusion, lacidipine protects stroke-prone hypertensive rats against the impairment of endothelium-dependent vasorelaxation evoked by a salt-rich diet, and this effect may contribute to its beneficial effect against end-organ damage and stroke.

Animals↗
PubMed1999

Functional reduction and associated cellular rearrangement in SHRSP rat basilar arteries are affected by salt load and calcium antagonist treatment.

The stroke-prone spontaneously hypertensive rat (SHRSP) is a strain with high incidence of cerebrovascular accidents increased by salt-rich diet and decreased by calcium-antagonist treatment. In the SHRSP rat basilar artery the authors have previously shown reduced contractility and altered structure including regions of smooth muscle cell (SMC) disorganization. The aims of this study have been to analyze (1) the morphology of these abnormal regions, (2) the structural modifications responsible for the reduced function, and (3) the effect of salt and calcium-antagonist treatment on vascular structure and function. Wistar Kyoto and SHRSP rats, untreated or treated from week 8 through 14 with 1% NaCl or 1% NaCl + 1 mg x kg(-1) x d(-1) lacidipine, were used. Function was studied with wire myography. Structure was analyzed in fixed intact arteries with confocal microscopy. Basilar arteries from SHRSP rat showed (1) reduced contractility, (2) discrete foci of SMC disarray with altered proportion of adventitia to SMC, and (3) decreased SMC and increased adventitial cell number. Arteries from salt-loaded SHRSP rats showed a higher degree of SMC disarray and further reduction in contractility. Lacidipine treatment of salt-loaded rats significantly improved structure and function. These data suggest that vascular remodeling can provide an explanation for the observed reduction in vascular contractility of SHRSP rat basilar arteries and might show light on the effects of salt load and calcium-channel blockers in life span and the incidence of cerebrovascular accidents in SHRSP rats.

Animals↗
PubMed1999

1,4-Dihydropyridine calcium channel blockers inhibit plasma and LDL oxidation and formation of oxidation-specific epitopes in the arterial wall and prolong survival in stroke-prone spontaneously hypertensive rats.

BACKGROUND AND PURPOSE: Calcium-channel blockers (CCBs) reduce systolic blood pressure and stroke-related mortality in stroke-prone spontaneously hypertensive rats (SPSHR). Brain ischemia is associated with loss of intracellular antioxidants. Increased formation of oxygen radicals and oxidation of LDL may enhance arterial vasoconstriction by various mechanisms. CCBs that also exert antioxidative properties in vitro may therefore be particularly useful. To investigate such antioxidant effects in vivo, we determined several parameters of LDL oxidation in SPSHR treated with two 1,4-dihydropyridine-type (1,4-DHP) CCBs of different lipophilic properties and compared them with antioxidant-treated and untreated controls. We also tested whether these drugs decrease the formation of oxidation-specific epitopes in arteries. METHODS: Five groups of 9 to 14 SPSHR each (aged 8 weeks) were treated with 80 mg/kg body wt per day nifedipine, 1 mg or 0.3 mg/kg body wt per day lacidipine, vitamin E (100 IU/d), or carrier for 5 weeks. A group of Wistar-Kyoto rats was used as normotensive control. Plasma samples were taken, and LDL was isolated by ultracentrifugation. Then LDL was exposed to oxygen radicals generated by xanthine/xanthine oxidase reaction (2 mmol/L xanthine+100 mU/mL xanthine oxidase), and several parameters of oxidation were determined. The presence of native apolipoprotein B and oxidation-specific epitopes in the carotid and middle cerebral arteries was determined immunocytochemically. RESULTS: 1,4-DHP CCBs completely prevented mortality. Normotensive Wistar-Kyoto rats showed less oxidation than control SPSHR. Plasma lipoperoxide levels were 0.87+/-0.27 micromol/L in control SPSHR, 0.69+/-0.19 and 0.63+/-0.20 micromol/L in the groups treated with 0.3 and 1 mg lacidipine, respectively, and 0.68+/-0.23 micromol/L in nifedipine-treated animals (P<0.05 versus control SPSHR for all values). Both CCBs significantly decreased formation of conjugated dienes and prolonged the lag time in LDL exposed to oxygen radicals. Similarly, lipoperoxides and malondialdehyde were significantly reduced (P<0.05). Reduced relative electrophoretic mobility and increased trinitrobenzenesulfonic acid reactivity of LDL from treated rats (P<0.01) also indicated that fewer lysine residues of apolipoprotein B were oxidatively modified in the presence of 1,4-DHP CCBs. Finally, these drugs reduced the intimal presence of apolipoprotein B and oxidized LDL (oxidation-specific epitopes) in carotid and middle cerebral arteries. CONCLUSIONS: In the SPSHR model, 1,4-DHP CCBs reduce plasma and LDL oxidation and formation of oxidation-specific epitopes and prolong survival independently of blood pressure modifications. Our results support the concept that the in vivo protective effect of these drugs on cerebral ischemia and stroke may in part result from inhibition of oxidative processes.

Animals↗
PubMed1998

A therapeutic dosage of amlodipine prevents vascular hyporeactivity induced in rats by lipopolysaccharide.

The aim of this work was to investigate whether treatment with the 1,4-dihydropyridine Ca2+ antagonist amlodipine could affect the vascular hyporesponsiveness induced by cytokines. Endotoxemia was induced by Salmonella typhosa lipopolysaccharide (LPS) injection (4 mg kg(-1), i.p.). In endothelium-denuded rings of thoracic aorta from untreated rats, contractile response to noradrenaline was decreased after LPS injection, this effect was partially overcome by the addition of N(omega)-nitro-L-arginine (L-NNA, 100 microM) into the bathing solution. In amlodipine-pretreated rats (15 mg kg(-1) day(-1), orally, for one week), the effect of LPS was lower than in untreated ones and it was completely reversed by L-NNA. The relaxation of the noradrenaline-induced tone evoked by L-arginine (10 microM) in aortae of LPS-injected rats was reduced in amlodipine-pretreated rats. Amlodipine-treatment reduced both the LPS-induced Ca2+-independent NOS activity in homogenates of heart and the expression of iNOS mRNA in aortae of LPS-injected rats. However, the vascular hyporeactivity induced by exposing aortae to interleukin-1beta in vitro was not influenced by amlodipine (10 nM). Amlodipine (10 microM) also did not affect the production of nitrite in primary aortic smooth muscle cell culture challenged by LPS although nitrite production in macrophage culture challenged with LPS was significantly inhibited. The results show that rat pretreatment with amlodipine prevented the decrease of vascular responsiveness induced by LPS, an effect that may be at least partly related to reduction of in vivo NOS induction. The weak effect of amlodipine on the in vitro NOS induction indicates that the protective action in endotoxemia did not result from a short term interaction with L-type Ca2+ channels in vascular smooth muscle. Alternative mechanisms are discussed.

Amlodipine↗
PubMed1997

Role of nitric oxide in the contractile response to 5-hydroxytryptamine of the basilar artery from Wistar Kyoto and stroke-prone rats.

1. Isolated basilar arteries from spontaneously hypertensive stroke-prone rats (SHRSP) are more sensitive to the contractile effect of 5-hydroxytryptamine (5-HT) than those from normotensive Wistar Kyoto rats (WKY). This has been attributed to a different proportion of 5-HT receptor subtypes mediating these responses. In the present study we have examined if differences in nitric oxide release could also contribute to this difference in sensitivity to 5-HT. 2. At rest, the normalized internal diameter was significantly smaller in SHRSP (297.4 +/- 3.5 microm, n = 88) than in WKY (375.1 +/- 4.0 microm, n = 62, P<0.01) arteries. The contractile response to 100 mM KCl was higher in WKY (3.57 +/- 0.15 mN mm(-1), n = 22) than in SHRSP arteries (2.32 +/- 0.20 mN mm(-1), n = 28, P<0.01). 3. When added on the plateau of contraction to 5-HT (1 microM), acetylcholine (ACh, 3 microM) evoked significant relaxation in all preparations from WKY (n = 20), but only in 15 out of 26 preparations from SHRSP. The mean relaxations were 55.4 +/- 5.2% in WKY and 20.6 +/- 4.6% in SHRSP (as % of the contractile tone evoked by 5-HT: P<0.01). 4. The NO synthase inhibitor N(omega)-nitro-L-arginine (L-NOARG, 0.1 mM) produced a similar increase in tone in both WKY and SHRSP. This tone was equal (in % of the contractile response to 100 mM KCl) to 70.8 +/- 4.4% in WKY (n = 20) and 67.6 +/- 5.9% in SHRSP (n=26) and was reversed by L-arginine (1 mM) and by 1,4-dihydropyridine calcium channel blockers (10 nM nisoldipine, 10 nM lacidipine, 100 nM nifedipine). The L-NOARG-induced tone was absent when the arteries were bathed in phosphate-free Krebs (pH 7.4). 5. EC50 values of 5-HT were about four fold smaller in SHRSP than in WKY arteries (P<0.01). The maximal response to 5-HT (Emax) was higher than 100 mM KCl-contraction in SHRSP but not in WKY arteries. Removal of endothelium produced a shift to the left of the 5-HT curve in WKY, but not in SHRSP arteries. 6. When evoked in phosphate-free Krebs, the contractile responses to 5-HT showed tachyphylaxis, but the responses were reproducible by adding the agonist at 30 min intervals. In such conditions, EC50 values of 5-HT were about two fold smaller in SHRSP than in WKY arteries (P<0.01). In phosphate-free Krebs, the blockade of NO synthase did not change the contractile response to 100 mM KCl; it reduced EC50 and increased Emax of 5-HT in WKY, but not in SHRSP. 7. These results confirm that the sensitivity to 5-HT is higher in basilar artery isolated from SHRSP than in those from WKY. They show that endothelium-dependent vasorelaxation to ACh is impaired in SHRSP. The finding that removal of endothelium or blockade of NO synthase augmented the contractile response to 5-HT in WKY, but not in SHRSP basilar arteries indicates that the difference in responsiveness to 5-HT observed between WKY and SHRSP basilar arteries might be, at least in part, related to dissimilarities in NO release. Furthermore, the L-NOARG-induced contraction sensitive to calcium channel blockers indicates that, in basilar arteries, NO production might lower L-type calcium channel opening and thereby control the tone of the vessels.

Acetylcholine↗
PubMed1997

[Preclinical study of the action of a calcium channel blocker during salt load].

Cardiovascular hypertrophy is a common feature of hypertension, but it is not known if this is related only to increased blood pressure or also to non-hemodynamic factors. Indeed, drug treatment of hypertension with hydralazine does reduce blood pressure but not cardiovascular hypertrophy. We used Stroke-prone rats (SHRSP) who are sensitive to salt load in order to better characterize the action of an antihypertensive agent on salt-dependent vascular hypertrophy and change in reactivity of calcium channels. SHRSP were submitted to salt load from 8 to 14 weeks of age with or without lacidipine, a long acting dihydropyridine. We observed that the cardiovascular hypertrophy was attenuated by lacidipine 0.3 mgkg-1 day-1 which did not change high blood pressure. The action of 1 mgkg-1 day-1 was higher on hypertrophy but, in addition, it reduced blood pressure. The salt-related increase in vascular responsiveness to the calcium channel activator Bay K 8644 was blunted by lacidipine treatment in both basilar and mesenteric arteries. By contrast with basilar artery, in mesenteric artery, this increased responsiveness was insensitive to bosentan, an endothelin antagonist but could be related to smooth muscle cell depolarization inhibited by lacidipine treatment. The present results confirm that lacidipine has blood pressure-independent effect on tissue remodeling in hypertension. They show that vascular response to salt is heterogeneous among vessels but is equally sensitive to lacidipine.

Animals↗
PubMed1996

Calcium antagonists and endothelial function: focus on nitric oxide and endothelin.

This paper reports on some interactions of calcium antagonists with nitric oxide and endothelin. It reviews evidence showing that the vasorelaxant action of calcium antagonists is facilitated by nitric oxide and describes the mechanism of this modulation. The interaction of calcium antagonists with endothelin is examined considering functions and production of the peptide. Among the functions examined, attention is drawn to the potentiation of responses to vasoconstrictors evoked by low threshold concentrations of endothelin, an action that could be important in pathology. The production of endothelin is increased by a high-salt diet in spontaneous hypertensive stroke-prone rats, this increased production, related to the overexpression of prepro ET-1mRNA, is responsible for cardiovascular hypertrophy and is blunted, in a blood pressure-unrelated manner, by the calcium antagonist lacidipine. At the same dosage regimen, lacidipine inhibits the hypertrophy of the cardiovascular system evoked by a high-salt diet.

Animals↗
PubMed1996

HIV-1, HIV-2, HTLV-I/II and STD among female prostitutes in Buenos Aires, Argentina.

To determine the prevalence of HIV-1 and HTLV-I/II among female prostitutes from different areas of the city of Buenos Aires, we studied serum samples from 237 individuals (mean age: 25; range 17 to 39). Prostitutes were recruited from 16 different Buenos Aires locations with different economical status. Information on sexual behaviour, health and socioeconomic conditions was collected through a questionnaire. HIV-1 and HTLV-I/II antibodies (ab) were tested by ELISA (Abbott) and Particle agglutination (Fujirebio, Tokyo) respectively. Positive results were confirmed by immunofluorescence assay. Samples that were positive for HIV-1 antibodies were also tested for p24 antigen (Abbott). VDRL for syphilis was performed in all samples. Fifteen (6.3%) out of the 237 individuals were positive for HIV-1 antibodies. Moreover, 2 (0.8%) HIV-1 seropositive prostitutes were also positive for HTLV-I/II antibodies and for HIV p24-Ag. Even though PCR for HTLV-I/II was not performed, titration by IFA in these two samples suggests HTLV-I. Our serologic results indicate a relatively high HIV-1 infection among prostitutes working in Buenos Aires. As we previously mentioned for other risk groups, we found an association between HTLV-I/II and HIV-1 infection in this particular group. Although we did not find any significant difference between HIV-1 seropositivity and the variables analyzed through the questionnaire, the prevalence of HIV-1 infection was higher in prostitutes working in mask brothels ('sauna or massage houses') as compared with hotel or street prostitutes.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Facilitation of the vasorelaxant action of calcium antagonists by basal nitric oxide in depolarized artery.

We investigated the effect of NO/cyclic GMP pathway on the action of calcium antagonists (isradipine, nisoldipine, lacidipine, verapamil, diltiazem) in rat aorta exposed to 100 mM KCl. For this purpose constitutive NO synthase was blocked by using 100 microM N omega-nitro-L-arginine (L-NNA). The steady-state contractile response evoked by 100 mM KCl was enhanced when the basal NO release had been blocked. The combined effects of basal NO release and calcium antagonists resulted in an inhibition greater than additive. Concentrations of calcium antagonists producing 50% inhibition of contraction were about 3-fold lower in the presence of the basal NO release than in its absence (P < 0.01). 45Ca2+ influx stimulated by 100 mM KCl was not affected by the basal NO release, but was inhibited by isradipine and verapamil regardless of NO blockade. Thus, the facilitation of the action of calcium antagonists by NO/cyclic GMP pathway seemed not to be accompanied by a modification of their action on L-type calcium channels. To confirm this, we measured the contractile tension and the calcium signal in fura-2 loaded rings, pretreated with either verapamil or verapamil plus 8-bromo cyclic GMP (BrcGMP), and further exposed to increasing concentrations of extracellular Ca2+ ([Ca2+]o) in 100 mM KCl solution. The increase in cytosolic Ca2- ([Ca2+]cyt) evoked by increasing ([Ca2+]o) in rings pretreated with verapamil alone was not different from rings pretreated with verapamil plus BrcGMP. In contrast, the [Ca2+]o-contraction curve was significantly shifted to the right in rings pretreated with verapamil plus BrcGMP. These results show that the NO/cyclic GMP pathway facilitates the inhibitory effect of calcium antagonists on 100 mM KCl-evoked contraction. This phenomenon is not related to a modification of calcium channel blockade, but could result from the reduction of the sensitivity of contractile machinery to Ca2+ by cyclic GMP.

Animals↗
PubMed1996

Inhibition by bosentan, an endothelin antagonist, of the hypersensitivity to Ca2+ channel activator evoked by salt-loading in basilar artery of stroke-prone spontaneously hypertensive rats.

High salt diet dramatically decreases the life time of spontaneously hypertensive stroke-prone rats (SHRSP). This has been related to an increase in the incidence of stroke. We have investigated the influence of high salt diet on the reactivity to the Ca2+ channel activator Bay K 8644 of basilar artery isolated from SHRSP. The results show that the sensitivity of basilar artery to Bay K 8644 was increased by salt load and that this hypersensitivity was blunted by bosentan, an ETA/ETB antagonist.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1996

Action of the calcium channel blocker lacidipine on cardiac hypertrophy and endothelin-1 gene expression in stroke-prone hypertensive rats.

1. The tissue-protective effects of calcium channel blockers in hypertension are not well dissociated from their effect on systolic blood pressure (SBP). We have previously shown that lacidipine, a dihydropyridine-type calcium antagonist, reduced the cardiac hypertrophy and the cardiac endothelin-1 (ET-1) gene overexpression occurring in salt-loaded stroke-prone spontaneously hypertensive rats (SL-SHRSP), an effect occurring without systolic blood pressure (SBP) change. In the present study, we have examined whether this action was dose-related and if it could be associated with ET receptor changes. The action of lacidipine was also examined in control SHRSP and in Wistar Kyoto rats (WKY). 2. The daily dose of 0.3 mg kg-1 lacidipine which did not lower SBP but significantly prevented ventricle hypertrophy and cardiac preproET-1-mRNA expression in SL-SHRSP was inactive in control SHRSP. With the higher dose of lacidipine (1 mg kg-1 day-1), we observed a further reduction of cardiac hypertrophy and of ET-1 gene expression in SL-SHRSP and a significant effect on those parameters in control SHRSP but only a small reduction of SBP in both groups. 3. In WKY, salt loading did not induce change in SBP or increase of cardiac ET-1 gene expression and ventricle mass. In these normotensive rats, lacidipine (1 mg kg-1 day-1) did not modulate the basal preproET-1-mRNA expression and did not affect SBP or heart weight. 4. The maximum binding capacity (Bmax) and the dissociation constant (KD) of [125I]-ET-1 binding and the relative proportion of low- and high-affinity binding sites for ET-3 were not significantly affected by salt loading or lacidipine treatment in SHRSP. 5. These results show that lacidipine exerted a dose-related inhibition of ventricle hypertrophy and preproET-1-mRNA expression in SHRSP and indicate that this effect was unrelated to SBP changes. The dose-dependency of this inhibition suggests that salt-induced cardiac hypertrophy could be related to ET-1 gene overexpression. The results further show that ET receptor changes are not involved in the pathophysiological process studied here.

Animals↗
PubMed1995

Inhibition by lacidipine of salt-dependent cardiac hypertrophy and endothelin gene expression in stroke-prone spontaneously hypertensive rats.

Stroke-prone spontaneously hypertensive rats receiving a high salt diet were orally treated by the calcium antagonist lacidipine, at a dose which did not reduce systolic blood pressure. We observed that lacidipine inhibited the salt-induced cardiac hypertrophy and the concomitant increase of mRNA transcripts for preproendothelin-1 in ventricles. These data show that elevated blood pressure cannot necessarily account for cardiac hypertrophy and indicate that the therapeutic action of lacidipine is not only related to its haemodynamic properties, but also to the inhibition of the gene expression of growth factors such as endothelin.

Age Factors↗
PubMed1995

Influence of salt loading on the cardiac and renal preproendothelin-1 mRNA expression in stroke-prone spontaneously hypertensive rats.

Endothelin-1 is a potent vasoactive peptide which may play a role in the regulation of vascular resistance through its autocrine/paracrine effects. We have investigated the influence of salt loading on the renal and cardiac production of endothelin-1 in stroke prone spontaneously hypertensive rats, a classical model of hypertension. The results show that the dietary salt intake did not change systolic blood pressure nor the renal expression of the preproendothelin-1 mRNA but increased cardiac expression of the endothelin-1 gene transcript and a concomitant ventricular hypertrophy.

Animals↗
PubMed1995

Evidence for a direct interaction of thapsigargin with voltage-dependent Ca2+ channel.

The effect of thapsigargin, an inhibitor of the sarco-endoplasmic reticulum Ca(2+)-ATPase, on voltage-dependent Ca2+ channels has been investigated in the A7r5 cell line and in membrane preparations from rat aorta, heart and brain. Patch-clamp technique showed that, at micromolar concentrations, thapsigargin inhibited the L-type Ca2+ channel current in A7r5 cells. It depressed the current at all voltages without change in the steady state inactivation curve. The rates of inactivation of the Ca2+ current were highly variable among the cells suggesting that more than one component of L-type Ca2+ current coexist in A7r5 cells, differing in the kinetics of inactivation. Thapsigargin appeared to be more potent on the slower-inactivating Ca2+ current than on the faster-inactivating one. In the same range of concentrations, thapsigargin inhibited the specific binding of 3H(+)-isradipine in intact cells while 45Ca2+ uptake in intracellular stores of skinned cells was inhibited at nanomolar concentrations. The equilibrium dissociation constant of 3H(+)-isradipine was increased in the presence of thapsigargin as a result of an increase of the dissociation rate constant indicating that the inhibitory effect of the antagonist cannot be attributed to a simple competitive interaction with the dihydropyridine binding site. Maximum binding capacity was unaffected. A similar pattern of inhibition of 3H(+)-isradipine binding was observed in membrane preparations from rat aorta, heart and brain. Those results indicate that, at micromolar concentrations, thapsigargin inhibits the voltage-dependent Ca2+ current by a direct interaction with the L-type Ca2+ channels.

Animals↗