Biomedical subjects

D Henrion

Publications and source records attributed to D Henrion.

At least 55 records · Page 3Linked to original sources

PubMed1997

Impaired nitric oxide- and prostaglandin-mediated responses to flow in resistance arteries of hypertensive rats.

In human and experimental hypertension, flow (shear stress)-induced dilation in large arteries is attenuated and resistant to nitric oxide blockade. We tested the hypothesis that a defect in nitric oxide-and/or prostaglandin-dependent flow-induced dilation might occur in mesenteric resistance arteries from spontaneously hypertensive rats (SHR). We measured resistance mesenteric artery diameter in situ by intravital microscopy and simultaneously measured mesenteric arterial pressure in a collateral artery. The flow-diameter-pressure relationship was established in normotensive Wistar-Kyoto rats (WKY) and in SHR under control conditions and after endothelium removal, inhibition of nitric oxide synthesis with N omega-nitro-L-arginine methyl ester (10 micromol/L), or inhibition of prostaglandin synthesis with indomethacin (10 micromol/L). Production of prostaglandins was determined in the perfusate. Endothelium removal decreased artery diameter by 14 +/- 1.6% in WKY and 5 +/- 0.5% (P<.01 versus WKY) in SHR at a flow rate of 400 microL/min. In WKY, N omega-nitro-L-arginine methyl ester and indomethacin decreased resistance artery diameter by 12 +/- 3% (P<.001) and 5 +/- 2% (P<.01), respectively, at a flow rate of 400 microL/min; neither substance had any significant effect in SHR. In both strains, flow induced the production of 6-keto-prostaglandin F1alpha, the metabolite of prostacyclin; prostaglandin F2alpha; and thromboxane B2, the stable metabolite of thromboxane A2. Production of 6-keto-prostaglandin F1alpha and prostaglandin F2alpha was significantly lower in SHR than WKY, and TxB2 production was significantly higher in SHR than WKY. The present findings suggest that in SHR mesenteric resistance arteries, dilation in response to increases in flow was resistant to nitric oxide and prostaglandin synthesis blockade. A modification of the ratio of vasodilator to vasoconstrictor prostaglandins might be at least partly responsible for the decreased dilator response to flow in SHR.

Animals↗

PubMed1997

In vitro modulation of a resistance artery diameter by the tissue renin-angiotensin system of a large donor artery.

A local renin-angiotensin system (RAS) is present in the vasculature and might have an important role in the control of vascular resistance. In order to assess its functional role in the control of vasomotor tone, we investigated the effect of the RAS of a donor vessel (rat carotid artery) on the diameter of a recipient rat mesenteric resistance artery. Arteries were perfused in series in an arteriograph at a rate of 100 microL/min, under a pressure of 100 mm Hg. The two vessels were superfused in separate organ chambers to which drugs were added. Recipient artery internal diameter was measured continuously. Phenylephrine (0.1 mumol/L) was present in the organ baths throughout the experiments, ensuring a preconstriction of the recipient artery (236 +/- 4 to 174 +/- 3 microns, n = 65 arterial segments from 34 rats). The angiotensin I-converting enzyme inhibitors (ACEIs) cilazapril (1 mumol/L) and captopril (10 mumol/L) inhibited phenylephrine-induced constriction by 30 +/- 12% (n = 7, P < .001) and 20 +/- 8% (n = 5, P < .01), respectively. Addition of cilazapril (1 mumol/L) or captopril (10 mumol/L) to the donor vessel chamber further inhibited the constriction by 8 +/- 3% (n = 7, P < .01) and 31 +/- 10% (n = 5, P < .05), respectively. The angiotensin II receptor (AT1) antagonist losartan (10 mumol/L) prevented, in part, the relaxation due to the ACEI. The association of losartan (10 mumol/L) with the bradykinin B2 receptor antagonist HOE 140 (1 mumol/L) totally prevented the relaxation due to the ACEI. Finally, angiotensin II was measured in the perfusate of the carotid artery and was found to be released at a rate of 11.9 +/- 2.2 pg in 60 minutes (n = 8), which was significantly decreased to 1.4 +/- 0.4 pg in 60 minutes (n = 4) by cilazapril (1 mumol/L). This study provides functional evidence that tissue-generated angiotensin II and bradykinin, produced locally and in upstream arteries, control the diameter of a resistance mesenteric artery.

Animals↗

PubMed1996

Chronic blockade of AT2-subtype receptors prevents the effect of angiotensin II on the rat vascular structure.

Angiotensin II (Ang II) is both a vasoactive and a potent growth-promoting factor for vascular smooth muscle cells. Little is known about the in vivo contribution of AT1 and AT2 receptor activation to the biological action of Ang II. Therefore, we investigated the effect of AT1 or AT2 subtype receptor chronic blockade by losartan or PD123319 on the vascular hypertrophy in rats with Ang II-induced hypertension. Normotensive rats received for 3 wk subcutaneous infusions of Ang II (120 ng/kg per min), or Ang II + PD 123319 (30 mg/kg per d), or Ang II + losartan (10 mg/kg per d) or PD 123319 alone, and were compared with control animals. In normotensive animals, chronic blockade of AT2 receptors did not affect the plasma level of angiotensin II and the vascular reactivity to angiotensin II mediated by the AT1 receptor. Chronic blockade of AT1I in rats receiving Ang II resulted in normal arterial pressure, but it induced significant aortic hypertrophy and fibrosis. Chronic blockade of AT2 receptors in Ang II-induced hypertensive rats had no effect on arterial pressure, but antagonized the effect of Ang II on arterial hypertrophy and fibrosis, suggesting that in vivo vasotrophic effects of Ang II are at least partially mediated via AT2 subtype receptors.

Angiotensin II↗

PubMed1996

Chronic infusion of low-dose angiotensin II potentiates the adrenergic response in vivo.

OBJECTIVE: The aim of this study was to investigate the role of angiotensin II-induced potentiation of the alpha 1-adrenergic contractile response in the aetiology of low-dose angiotensin II-induced hypertension. METHODS: Wistar rats (250g) received angiotensin II (120 ng/kg per min) from subcutaneous minipumps for 21 days. The responses of vaso-active properties of second-order mesenteric arteries (200 micron) to potassium, phenylephrine, angiotensin II and acetylcholine were assessed. The acute amplification effects of angiotensin II on the response to phenylephrine were examined. RESULTS: Angiotensin II induced a progressive hypertension, which reached a plateau after approximately 5 days. The responses to potassium, angiotensin II and acetylcholine were not significantly modified in rats treated chronically with angiotensin II. The major finding of this study is that the response to phenylephrine (1-3 mumol/l) was potentiated (sevenfold at 1.75 mumol/l) after chronic treatment with angiotensin II. In control vessels acute addition of angiotensin II (10(-10) mol/l) produced no contraction but induced potentiation of the phenylephrine response (1-3 mumol/l). No further potentiation of the phenylephrine response was observed in the rats treated chronically with angiotensin II. CONCLUSIONS: Thus, although the direct contractile responses to potassium and angiotensin II remain unaffected following chronic angiotensin II treatment, the alpha 1-adrenergic contractile response to phenylephrine is significantly potentiated by angiotensin II in this model of hypertension. We suggest that this potentiation contributes to the hypertension observed in response to infusion of low-dose angiotensin II.

Acetylcholine↗

PubMed1996

Vascular reactivity in mesenteric resistance arteries following chronic nitric oxide synthase inhibition in Wistar rats.

1. Chronic inhibition of nitric oxide synthase (NOS) induces a sustained hypertension in rats. We studied the effects of chronic inhibition on the in vitro vasoreactivity of mesenteric resistance arteries in Wistar rats. We also investigated the effects of acute in vitro NOS inhibition in these vessels. 2. Acute NOS inhibition (N omega-nitro-L-arginine, L-NOARG, 10 microM) had no effect on the contractile response to KCl (125 mM), enhanced the response to the phorbol ester, phorbol dibutyrate (1 microM; 69 +/- 9% of KCl response, n = 6; 38 +/- 7% control, n = 6, P < 0.05), increased sensitivity to phenylephrine (EC50: 1.68 +/- 0.14 microM, n = 5; 2.35 +/- 0.23 microM control, n = 5, P < 0.05) and sodium nitroprusside (SNP; EC50 1.79 +/- 0.61 nM, n = 6; 20.44 +/- 6.87 nM control, n = 6, P < 0.05) and decreased sensitivity to acetylcholine (EC50 123 +/- 12 nM, n = 6; 45 +/- 10 nM control, n = 13, P < 0.05). 3. In contrast, contractile responses to KCl (125 mM; 170 +/- 12 mN mm-3, n = 10; 257 +/- 21 mN mm-3 in control, n = 13, P < 0.005) and phenylephrine (maximum response, 30 microM: 169 +/- 24 mN mm-3, n = 10; 295 +/- 19 mN mm-3 in control, n = 13, P < 0.001) were significantly reduced in magnitude following chronic NOS inhibition. Sensitivity to phenylephrine was not significantly altered. 4. The effects of chronic NOS inhibition (N omega-nitro-L-arginine methyl ester, L-NAME, 10 mg kg-1 daily for 3 weeks) were similar to those of acute NOS blockade with respect to the relaxant responses to SNP and acetylcholine, and also the contraction in response to protein kinase C activation. 5. Chronic inhibition of NOS significantly increased medial cross sectional area of mesenteric resistance arteries (0.013 +/- 0.002 mm2, n = 7; 0.009 +/- 0.0005 mm2 control, n = 15, P < 0.05). 6. Thus, in contrast to the acute effects of NOS inhibition, chronic NOS inhibition results in a down-regulation of the contractile responses to KCl and phenylephrine in mesenteric resistance arteries, despite an increase in medial cross sectional area. However protein kinase C-dependent contraction remains relatively enhanced. Endothelium-dependent relaxation is reduced and endothelium-independent relaxation is enhanced in a manner similar to the effects of acute NOS blockade.

Animals↗

PubMed1996

Role of NO in flow-induced remodeling of the rabbit common carotid artery.

Flow-induced changes in vessel caliber tend to restore baseline wall shear stress (WSS) and have been reported to be endothelium-dependent. To investigate the role of endothelium-derived nitric oxide (NO) in the adaptive increase in artery diameter in response to a chronic increase in blood flow, an arteriovenous fistula was constructed between the left common carotid artery (CCA) and the external jugular vein in 22 New Zealand White rabbits, and NO synthesis was inhibited in 14 animals by long-term administration of NG-nitro-L-arginine-methyl ester (L-NAME) in drinking water given for 4 weeks. The remaining 8 animals served as controls. Mean arterial blood pressure was not significantly altered by L-NAME treatment (91 +/- 2 in control versus 98 +/- 3 mm Hg in L-NAME-treated rabbits). Blood flow significantly increased in the left CCA in both groups but was lower in L-NAME-treated than control animals (106.1 +/- 10.7 versus 196.2 +/- 32.3 mL/min, P < .003). The diameter of the flow-loaded left CCA also increased significantly in both groups compared with the right CCA (2.15 +/- 0.12 and 2.54 +/- 0.1 mm, respectively, P < .02), but the increase was less in the L-NAME-treated than the control group (3.24 +/- 0.09 and 4.64 +/- 0.17 mm, respectively, P < .0001). The diameter of the anastomosed veins was also increased but to a much lesser degree in L-NAME-treated animals than in controls (4.14 +/- 0.29 versus 7.94 +/- 0.51 mm, P < .0001). As a result of artery enlargement, WSS was normalized in the flow-loaded left CCA of the control group (8.87 +/- 0.77 dynes/cm2) regardless of blood flow values. In L-NAME-treated animals, however, WSS was only partially regulated, the mean value being significantly increased (18.7 +/- 2.2 dynes/cm2, P < .006). Moreover, a highly significant positive correlation between WSS and blood flow was obtained in L-NAME-treated animals (r = .84, P < .0001). We also found remodeling of the artery wall, with a larger increase in the medial cross-sectional area associated with an increased number of smooth muscle cells, in the control group compared with the L-NAME-treated group (0.75 +/- 0.09 versus 0.49 +/- 0.04 mm2 and 4504 +/- 722 versus 2717 +/- 282 cells/mm2, P < .03). We conclude that NO plays a role in the increase of vessel caliber in response to chronic increase in blood flow. As yet unidentified additional metabolic processes appear to be necessary for a complete regulatory response.

Administration, Oral↗

PubMed1996

In vitro alteration of aortic vascular reactivity in hypertension induced by chronic NG-nitro-L-arginine methyl ester.

Chronic administration of NG-nitro-L-arginine methyl ester (L-NAME) induces a rise in blood pressure that is prevented by angiotensin I-converting enzyme inhibitors or angiotensin II receptor (type 1) blockade. Alterations in vascular reactivity in this model have not been extensively studied and could potentially be involved in the pathogenesis of L-NAME-induced hypertension. In the present work, we aimed to study the vascular reactivity and cGMP content of aortic ring segments isolated from Wistar rats treated for 3 weeks with L-NAME or L-NAME plus the converting enzyme inhibitor quinapril. Quinapril prevented the rise in blood pressure in L-NAME-treated rats although acetylcholine-induced dilation in aortic rings was suppressed and sodium nitroprusside-induced dilation was increased in both L-NAME- and L-NAME plus quinapril-treated rats. In isolated aortic ring segments, chronic L-NAME decreased the contractile response to K+ (125 mmol/L), phenylephrine, angiotensin II, the G protein stimulator AlF4-, and the protein kinase C activator phorbol dibutyrate. In contrast to the upregulated sodium nitroprusside-induced dilation, the contractile capacity of the aorta in response to angiotensin II, phenylephrine, AlF4-, K+, and phorbol dibutyrate was restored by quinapril. Aortic cGMP was lowered in rats treated with L-NAME (530 +/- 120 fmol/mg protein, n = 12, P < .05) and L-NAME plus quinapril (461 +/- 140 fmol/mg protein, n = 12, P < .05) compared with controls (1798 +/- 522 fmol/mg protein, n = 12). We hypothesize that the continuous nitric oxide blockade by L-NAME might attenuate a continuous endogenous relaxing tone and is associated with an upregulated endogenous vasoconstrictor tone in large arteries. Converting enzyme inhibition interfered more with the increased endogenous constrictor tone than with the decreased vasodilator tone in the wall of large arteries from L-NAME-treated rats.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1994

Insulin potentiates norepinephrine-induced vascular tone by activation of protein kinase C and tyrosine kinase.

Insulin might play a role in the hypertension occurring in insulin-resistant diabetes. In addition, insulin has recently been shown to potentiate norepinephrine (NE) induced vascular tone. We used ring segments of the rabbit facial artery mounted in a myograph to test the hypothesis that potentiation of NE-induced tone by insulin may be related to activation of protein kinase C (PKC) and tyrosine kinase (TK). NE-induced contractions in the presence of insulin (1 mU/mL) were 200% (NE 0.1 and 0.3 microM), 252% (NE 1 microM), and 129% (NE 3 microM) of control. Insulin (1 mU/mL) had no effect on NE (10 and 100 microM) induced contractions. The potentiation by insulin of NE-induced tone was not altered by endothelium removal and could be mimicked by phorbol-12-myristate-13-acetate (PMA, 0.1 microM). Histamine-induced contractions were not altered by insulin (1 mU/mL). Insulin potentiation of NE-induced tone was suppressed by pretreatment of the rabbit facial artery with the PKC inhibitor calphostin C (0.1 microM) or the TK inhibitor genistein (10 microM). 45Ca2+ influx due to NE (3 microM) did not change in the presence of insulin (1 mU/mL) or PMA (0.1 microM) despite a higher contractile response, so that wall force per unit of 45Ca2+ influx was increased by insulin (1 mU/mL) and PMA (0.1 microM). Calphostin C (0.1 microM) and genistein (10 microM) both prevented the increase in wall force per unit of 45Ca2+ influx due to insulin (1 mU/mL). Our study shows that insulin potentiates NE-induced tone through a TK- and PKC-dependent mechanism.

Animals↗

PubMed1994

Pharmacological implications of the flow-dependence of vascular smooth muscle tone.

The recognition that the wall tone of most arteries and veins can change in response to shear stress has several implications for our understanding of the effects of drugs on the circulation. By a primary action on the heart and vasculature, drugs can cause changes in cardiac output and blood pressure that lead to changes in blood flow. These changes in blood flow can secondarily change vascular diameter, thus complicating the basic response. Furthermore, drugs can modify the local flow-sensitive mechanism directly. The flow-initiated effect seems to depend, both qualitatively and quantitatively, on the level of wall tone and is not entirely endothelium-dependent. If the primary action of a drug is to alter the tone level of vascular smooth muscle directly or if tone changes as a result of a change in blood pressure (and thus in local myogenic control), then it follows that these changes in turn influence the flow response, both quantitatively and qualitatively. The vascular response to flow is complex both in its site of origin and the functional changes initiated. It is not synonymous with the endothelial-dependent action of acetylcholine.

Animals↗

PubMed1994

Myogenic tone of rabbit facial vein and posterior cerebral artery is influenced by changes in extracellular sodium.

We examined the effect of small changes in extracellular Na+ concentration ([Na+]e) on myogenic tone (MT) in isometrically mounted ring segments of the rabbit facial vein and in pressurized cannulated posterior cerebral artery segments. Decreasing [Na+]e from 150 to 120 mM in the vein increased MT by 24%, and raising [Na+]e to 165 mM attenuated it by 30%. In pressurized posterior cerebral arteries, decreasing [Na+]e to 120 mM reduced the intraluminal diameter by 12%, whereas increasing [Na+]e to 165 mM increased it by 17%. MT was inhibited by amiloride [50% inhibitory concentration (IC50) = 17 +/- 6 microM], an inhibitor of Na(+)-H+ exchange. Diisothiocyanatostilbene sulfonic acid, a Na(+)-Cl(-)-HCO3- cotransporter blocker, inhibited MT with an IC50 of 4.4 +/- 0.65 microM. Ouabain increased MT [50% effective concentration (EC50) = 0.10 +/- 0.04 microM] as did the reintroduction of HCO3- (EC50 5.0 +/- 1.5 mM). Our study suggests that MT in the rabbit posterior cerebral artery and rabbit facial vein is modulated by changes in [Na+]e. This effect is independent of the method used to register changes in wall force. The sensitivity of the tone to changes in [Na+]e and the independence of vessel diameter at different pressures at various [Na+]e may reflect changes in the sensitivity of smooth muscle stretch or mechanoreceptors to [Na+]e.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1994

Endogenous angiotensin II enhances phenylephrine-induced tone in hypertensive rats.

Subthreshold concentrations of angiotensin II (Ang II) potentiate agonist-induced tone in a variety of blood vessels. We measured in vivo the mesenteric artery diameter and blood flow in 12-week-old normotensive Wistar-Kyoto (WKY) rats (n = 20) and spontaneously hypertensive rats (SHR, n = 20); systemic blood pressure was monitored continuously. Phenylephrine (10 mumol/L) superfused on the exteriorized mesentery reduced arterial diameter from 480 +/- 40 to 256 +/- 18 microns (P < .05) in WKY rats and from 562 +/- 26 to 273 +/- 7 microns (P < .05) in SHR, whereas blood flow was lowered by 77% in WKY rats and 76% in SHR (P < .05 in both strains). Topical superfusion of an angiotensin-converting enzyme inhibitor (perindoprilat, 10 and 100 mumol/L) attenuated the phenylephrine-induced decrease in diameter and blood flow in both strains (P < .05). The Ang II type 1 receptor blocker losartan (10 mumol/L) attenuated the phenylephrine-induced decrease in diameter and blood flow in both strains (P < .05). The relaxing effect of losartan was significantly accentuated by the addition of perindoprilat (10 mumol/L) to the superfusate (P < .05 in both strains). Systemic blood pressure was unaffected by the topical application of phenylephrine (10 mumol/L), perindoprilat (10 or 100 mumol/L), or losartan (10 mumol/L). We conclude that phenylephrine-induced tone impairment by angiotensin-converting enzyme inhibition and Ang II type 1 receptor blockade in vivo probably reflects the role of endogenous Ang II in the potentiation of the adrenergic response during the control of vascular tone. This role is identical in both normotensive and hypertensive rats.

Angiotensin II↗

PubMed1994

Alterations in flow-dependent vasomotor tone in spontaneously hypertensive rats.

We studied the effect of endothelium on the flow-induced response of conductance arteries and the resistance arteriolar network in an in situ model of perfused mesenteric artery in normotensive Wistar-Kyoto and spontaneously hypertensive rats. The mesenteric network was perfused with a Tyrode's albumin solution. The diameter of a conductance mesenteric artery was measured using a video camera system, and mesenteric pressure was recorded in a collateral artery. The preparation was perfused at 0.2, 2, and 4 mL/min, and flow-diameter-pressure relations were established (1) under control conditions, (2) during local inhibition of nitric oxide synthesis by topical application of N omega-nitro-L-arginine methyl ester (L-NAME) (1 mmol/L), and (3) after endothelium removal (CO2 drying). In normotensive rats, L-NAME decreased conductance artery diameter by 12 +/- 2% (P < .01) at 0.2 mL/min and 3.3 +/- 1.9% (P < .05) at 2 mL/min. In hypertensive rats, L-NAME did not modify mesenteric diameter. Endothelium removal markedly increased arterial resistance in both strains and decreased conductance artery diameter in normotensive rats (10.3 +/- 3%, P < .05 at 0.2 mL/min and 4.2 +/- 2%, P < .05 at 2 mL/min) but not in hypertensive rats. The present study suggests that the endothelium plays a similar role in the control of mesenteric resistance in both strains and that there is a significant diameter-flow dependency affected by both endothelium removal and inhibition of nitric oxide synthesis in conductance mesenteric arteries from normotensive but not from hypertensive rats.

Animals↗

PubMed1993

Effects of staurosporine and calphostin C, two structurally unrelated inhibitors of protein kinase C, on vascular tone.

In isolated rings of the rabbit facial vein, facial artery, and aorta, calphostin C and staurosporine, inhibitors of protein kinase C, reduced myogenic tone and norepinephrine (1 microM), K+ (80 mM), and Ca2+ (1.6 mM) induced tone. In all instances, staurosporine was more potent than calphostin C. In contrast to staurosporine, the IC50 value of calphostin C against myogenic tone was similar to that recorded for protein kinase C in biochemical studies (0.086 vs. 0.050 microM) and the average IC50 values of calphostin C against norepinephrine (2.2 microM), K+ (3.3 microM), and Ca2+ (4.3 microM) in the three vessels were similar to that for myosin light-chain kinase in biochemical studies (> 5.0 microM). In the facial vein, calphostin C was 59-fold more potent against myogenic tone than against Ca(2+)-induced tone and 8-fold more specific for myogenic tone than was staurosporine. In addition, at concentrations not affecting K+ (80 mM) induced tone, calphostin C suppressed 1-oleoyl-2-acetyl-sn-glycerol induced tone in the facial vein, whereas staurosporine only attenuated it by 65%. Thus calphostin C inhibits protein kinase C dependent tone in isolated blood vessels to a greater extent than does staurosporine.

Alkaloids↗

PubMed1993

Potentiation of norepinephrine-induced contractions by endothelin-1 in the rabbit aorta.

Subthreshold concentrations of endothelin-1 potentiated the norepinephrine-induced contraction in isometrically mounted rings of the rabbit aorta. Pretreatment with endothelin-1 (0.1 nM) for 10 minutes increased the sensitivity of the aortic rings to norepinephrine without affecting the maximal contraction. This amplification was unaffected by removal of the endothelium but was prevented by the protein kinase C inhibitors staurosporine (0.01 microM) and calphostin C (0.1 microM). Pretreatment of the aortic rings for 24 hours with phorbol 12-myristate 13-acetate (0.1 microM) also abolished the potentiation. Norepinephrine-induced contraction was potentiated by pretreating with phorbol 12-myristate 13-acetate (10 nM) and by increasing the concentration of K+ in the bath solution from 4.6 to 8.6 mM. The potentiation of the norepinephrine-induced contraction by endothelin-1 (0.1 nM) or by phorbol 12-myristate 13-acetate (10 nM) was not associated with an increase in norepinephrine-induced 45Ca2+ uptake or influx, whereas the potentiation due to an increase in the concentration of K+ in the bath solution from 4.6 to 8.6 mM was associated with an increase in norepinephrine-induced 45Ca2+ uptake. We conclude that endothelin-1 potentiation of the norepinephrine-induced contraction occurs in the absence of changes in stimulated Ca2+ entry and is endothelium independent. It is probable that endothelin-1 increases the sensitivity of the contractile apparatus to Ca2+ by activating protein kinase C-dependent mechanisms.

Alkaloids↗

PubMed1992

Further evidence from an elastic artery that angiotensin II amplifies noradrenaline-induced contraction through activation of protein kinase C.

Angiotensin II (AII, 0.1 nM) increased concentration dependently the sensitivity of rabbit aortic rings to low concentrations of noradrenaline. This was not associated with increases in noradrenaline-induced 45Ca2+ uptake or efflux and was prevented by the protein kinase C (PKC) inhibitors staurosporine (0.01 microM) and calphostin C (0.1 microM). Pretreatment of the rings with PMA (phorbol-12-myristate-13-acetate, 0.1 and 1 microM, 24 h at 4 degrees C) abolished the potentiation phenomenon. We conclude that AII potentiation of noradrenaline-induced vascular tone may be due to a PKC-mediated increase in intracellular sensitivity of the contractile apparatus to Ca2+.

Alkaloids↗

PubMed1992

Intraluminal flow increases vascular tone and 45Ca2+ influx in the rabbit facial vein.

The buccal segment of the rabbit facial vein exhibits a high level of myogenic tone in vitro that develops only in stretched vessel segments between 33 degrees and 44 degrees C. The infusion of physiological salt solution into the lumen of 2-mm-long rabbit facial vein segments induced a flow rate-dependent increase in wall tone, both in the presence (37 degrees C) and absence (30 degrees C) of myogenic tone. In calcium-free physiological solution with EGTA, neither flow nor stretch-induced tone was observed. This flow-induced contraction was associated with an increase in 45Ca2+ unidirectional influx and net uptake. These measurements correlated positively with the level of the associated constrictor responses, both in the presence or absence of myogenic tone. The mean contractile responses to flow (10 and 40 microliters/min), stretch, and histamine (1 microM) were 13%, 28%, 24%, and 33% of the tissue maximal response, respectively. When 45Ca2+ influx was expressed in relation to the force development (45Ca2+ influx per milligram), the amount of calcium entry was dependent on the stimulus. Values for 45Ca2+ influx per milligram in response to flow (10 and 40 microliters/min) and to histamine (1 microM) were not significantly different. The value was significantly lower for the response to stretch. On the other hand, 45Ca2+ net uptake, when expressed per unit force, was similar in response to flow (10 and 40 microliters/min), histamine (1 microM), and stretch.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Effect of chronic treatment with the calcium entry blocker, isradipine, on vascular calcium overload produced by vitamin D3 and nicotine in rats.

Treatment of young rats with vitamin D3 and nicotine produced a 35-fold increase in the calcium content of the aorta and a 4-fold increase in the calcium content of the mesenteric arterial bed. Blood pressure was not modified. In vitro, aortic rings and mesenteric arterial bed preparations from such animals showed diminished vasoconstrictor responses to norepinephrine. After precontraction with norepinephrine, the endothelium-dependent vasodilator, carbachol, produced vasorelaxation. This latter effect was attenuated in aortic rings and mesenteric arterial bed preparations from animals previously treated with vitamin D3 and nicotine, but the vasodilator effect of sodium nitroprusside (which is independent of the endothelium) was unchanged. Prolonged treatment with the calcium entry blocker, isradipine, at a dose (1 mg/kg, i.p.) which had no effect on blood pressure, prevented calcium overload of the mesenteric arterial bed, but did not modify aortic calcium overload. Isradipine treatment had no effect on vasoconstrictor responses to norepinephrine in vitro. Such treatment did, however, restore the endothelium-dependent vasodilator effect of carbachol in the mesenteric arterial bed (but not in aortic rings). In conclusion, in a rat model of vascular calcium overload produced by administration of vitamin D3 plus nicotine, chronic treatment with a low dose of the calcium entry blocker, isradipine, restored the endothelium-dependent vasorelaxant effect of carbachol in the mesenteric arterial bed, but not in the aorta.

Animals↗

PubMed1992

Angiotensin II amplifies arterial contractile response to norepinephrine without increasing Ca++ influx: role of protein kinase C.

We investigated whether the enhanced contractile response to norepinephrine caused by a subthreshold concentration of angiotensin II was associated with an increased 45Ca++ influx or net uptake. Rabbit facial artery segments were mounted isometrically to measure the 45Ca++ influx and net uptake in response to norepinephrine. The contractile response to norepinephrine (3 microM) in the presence of angiotensin II (0.1 nM) was 149.5 +/- 7.4% of control. This response amplification was not associated with changes in norepinephrine-induced 45Ca++ influx or net uptake. Angiotensin II also potentiated the contractile response to caffeine obtained in a Ca(++)-free buffer containing ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid (2 mM) to 148.0 +/- 4.8% of control. In both cases, the amplification was prevented by pretreatment with either staurosporine (10 nM) or calphostin C (100 nM), two inhibitors of protein kinase C. We conclude that angiotensin II potentiation of norepinephrine-induced vascular tone occurs in the absence of changes in stimulated Ca++ entry. This potentiation may be due to an increase in intracellular sensitivity to Ca++, possibly mediated by protein kinase C.

Alkaloids↗