Biomedical subjects

R D Bukoski

Publications and source records attributed to R D Bukoski.

At least 37 records · Page 2Linked to original sources

PubMed1996

Agonists increase the sensitivity of contractile elements for Ca++ in pregnant rat myometrium.

OBJECTIVE: The effects of agonists and guanosine 5'-triphosphate binding proteins (G proteins) on contractile properties were investigated in rat longitudinal myometrial tissues in late gestation and during delivery. STUDY DESIGN: The effect of carbachol was examined on the intracellular Ca++ concentration in intact thin muscle strips from pregnant rat myometrium. In addition, the action of carbachol with guanosine 5'-triphosphate was examined on the Ca(++)-induced contractions in beta-escin-treated skinned strips (membrane-permeable conditions and chemical clamping of intracellular Ca++ concentrations). The effects of guanosine 5'-0-(gamma-thiotriphosphate) (a nonhydrolyzable analog of guanosine 5'-triphosphate), prostaglandin F2 alpha with guanosine 5'-triphosphate, prostaglandin E2 with guanosine 5'-triphosphate, and okadaic acid (a phosphatase inhibitor) were also examined in skinned strips. RESULTS: In intact longitudinal rat myometrium at late gestation the maximum contractions induced by carbachol were larger than the maximum contractions induced by high K+ (118 mmol/L), whereas increases in intracellular Ca++ concentration produced by both agents were similar. In beta-escin-treated skinned myometrial strips from late gestation, 0.3 mumol/L Ca++ evoked contractions. Carbachol (10 mumol/L) plus guanosine 5'-triphosphate (10 mumol/L) enhanced the 0.3 mumol/L Ca(++)-induced contractions of skinned strips; the increase was antagonized by 1 mmol/L guanosine 5'-0-(beta-thiodiphosphate). Guanosine 5'-0-(gamma-thiotriphosphate) (0.1 to 100 mumol/L), prostaglandin F2 alpha (10 mumol/L) plus guanosine 5'-triphosphate (10 mumol/L), prostaglandin E2 (10 mumol/L) plus guanosine 5'-triphosphate (10 mumol/L), and okadaic acid (1 nmol/L) also augmented 0.3 mumol/L Ca++ contractions in skinned strips. The increases of 0.3 mumol/L Ca(++)-induced contractility by the agonists with guanosine 5'-triphosphate or guanosine 5'-0-(gamma-thiotriphosphate) were similar between late gestation and delivery. CONCLUSION: These results suggest that agonists such as carbachol, prostaglandin F2 alpha, and prostaglandin E2 enhance the Ca(++)-induced contraction of myometrium at late gestation through G protein-mediated mechanisms. The agonist/G protein-mediated Ca(++)-sensitizing effects on contractile elements produce additional contractile force with the same amount of intracellular calcium, thus providing expelling forces for delivery of the fetuses.

Animals↗

PubMed1996

1,25(OH)2D3 modulates intracellular Ca2+ and force generation in resistance arteries.

The mechanism by which 1 alpha,25-dihydroxycholecalciferol [1,25(OH)2D3] enhances smooth muscle force generation was examined. Rats were injected on three mornings with 1,25(OH)2D3 (35 ng/100 g) or vehicle, and on the fourth morning mesenteric resistance arteries were isolated and used for simultaneous measurement of intracellular Ca2+ and force or myosin light chain phosphorylation. 1,25(OH)2D3 did not affect media thickness or wall-to-lumen ratio, but it increased basal intracellular Ca2+ (vehicle = 49.2 +/- 2.2 nM vs. 1,25(OH)2D3 = 65.9 +/- 4.0 nM, P < 0.05, n = 24-26 rats). 1,25(OH)2D3 enhanced the active stress and intracellular Ca2+ responses to increasing doses of norepinephrine, and the increases were normalized by verapamil (10 microM). In a second group of animals, 1,25(OH)2D3 significantly increased both basal intracellular Ca2+ and light chain phosphorylation and the active stress and Ca2+ mobilization responses to norepinephrine (10 microM). The hormone did not affect peak or steady-state light chain phosphorylation. Myofilament Ca2+ sensitivity, determined during stimulation with 2 microM norepinephrine, was depressed in vessels isolated from rats treated with 1,25(OH)2D3 [vehicle Ca2+ 50% effective dosé (ED50) = 82.7 +/- 3.8 nM vs. 1,25(OH)2D3 = 104.8 +/- 4.9 nM, P = 0.002]. We conclude that 1,25(OH)2D3 enhances resistance artery force generation by altering smooth muscle Ca2+ homeostasis, with effects on basal and verapamil-sensitive, agonist-induced Ca2+ mobilization.

Animals↗

PubMed1995

Differential expression and effect of 1,25-dihydroxyvitamin D3 on myosin in arterial tree of rats.

The hypothesis that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3, also known as calcitriol] modulates myosin expression in vascular smooth muscle was tested. Wistar-Kyoto or spontaneously hypertensive rats given intraperitoneal injections of 25 ng 1,25(OH)2D3/100 g body weight for varying periods of time showed a greater than twofold increase in aortic mRNA encoding the myosin regulatory light chain relative to 18S rRNA (P < 0.05). 1,25(OH)2D3 administration to Wistar rats caused a significant increase in the aortic content of total myosin regulatory light chain and total myosin heavy chain. The increase in myosin light chain was the result of a specific increase in expression of its smooth muscle isoform [control = 65.2 +/- 3.4% vs. 1,25(OH)2D3 = 78.7 +/- 3.6%, P = 0.020]. 1,25(OH)2D3 had no effect on total myosin light chain or heavy chain in the superior mesenteric artery. The hormone did, however, increase the proportion of the smooth muscle isoform of the light chain in this vessel [control = 81.4 +/- 2.6% vs. 1,25(OH)2D3 = 88.8 +/- 2.1%, P = 0.048]. In branch II and III mesenteric resistance arteries, 1,25(OH)2D3 significantly increased the active stress response to 10 mumol/l norepinephrine but was without effect on total myosin light chain or heavy chain content or on the relative expression of the myosin light chain isoforms [control = 94.0 +/- 1.4% vs. 1,25(OH)2D3 = 95.8 +/- 1.1%, P = 0.33].(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Modulation of resistance artery force generation by extracellular Ca2+.

We tested the hypothesis that increasing extracellular Ca2+ (Cao) over a physiological concentration range depresses vascular smooth muscle force generation by altering the intracellular Ca2+ (Cai)-force relationship. Mesenteric resistance arteries were isolated from Wistar rats; Cai and isometric force were measured using a fura-based method and wire myography. Vessels were depleted of releasable Cai by repeated contraction with norepinephrine; Cao was then cumulatively added back from 0.025-2.5 mM in the presence of an agonist. With norepinephrine, serotonin, prostaglandin F2 alpha, and K+, Cao from 0.025 to 0.8 mM induced a graded increase in Cai and active stress. With the receptor agonists but not K+ raising Cao from 0.8 to 1.6 mM and from 1.6 to 2.5 mM decreased active stress to 82 +/- 6 and 54 +/- 6% of maximum, respectively, P < 0.05. Although there was a transient decrease in Cai in response to both 1.6 and 2.5 mM Cao, steady-state Cai only decreased significantly in response to 2.5 mM Cao (85 +/- 3% of maximum). Inhibition of the sarcoplasmic reticulum Ca(2+)-adenosinetriphosphatase with 1 microM thapsigargin had no effect on the decrease in force induced by high Ca2+. The decrease in active stress induced by 1.6 and 2.5 mM Cao was inhibited by Ca2+ channel antagonists and by blockade of Ca(2+)-activated K+ channels with charybdotoxin (with 1.6 mM Cao, control tension = 67 +/- 10% of maximum vs. charybdotoxin = 99.2 +/- 1%, P < 0.05; n = 9).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Myofilament calcium sensitivity of normotensive and hypertensive resistance arteries.

We measured intracellular Ca2+ and isometric force simultaneously in endothelium-denuded mesenteric resistance arteries of 12- to 15-week-old male spontaneously hypertensive rats (SHR). Wistar-Kyoto (WKY) rats, and Wistar rats. Basal Ca2+ did not differ among vessels of these strains (SHR, 86.6 +/- 4.5 nmol/L; WKY, 78.5 +/- 4.7 nmol/L; Wistar, 83.1 +/- 3.9 nmol/L). Myofilament Ca2+ sensitivity was determined by measuring the intracellular Ca2+ and force responses to cumulative addition of extracellular Ca2+ (0.025 to 2.5 mmol/L) in the presence of 100 mmol/L K+ or 10 mumol/L norepinephrine after depletion of releasable intracellular Ca2+ stores. With 100 mmol/L K+, no between-strain differences in active stress, intracellular Ca2+, or myofilament Ca2+ sensitivity were observed. With 10 mumol/L norepinephrine, the active stress response of SHR vessels to 0.025 and 0.05 mmol/L Ca2+ was increased compared with both normotensive strains. The intracellular Ca2+ response was not different in vessels of SHR and WKY rats but was depressed in Wistar vessels. Myofilament Ca2+ sensitivity of SHR was elevated compared with both WKY and Wistar rats (P < .05) (ED25 for SHR, 74.4 +/- 5.1 nmol/L; WKY, 89.8 +/- 5.5 nmol/L; Wistar, 86.9 +/- 3.4 nmol/L). No strain differences in intracellular Ca2+ or active stress responses of SHR and WKY vessels were detected during cumulative addition of norepinephrine with constant extracellular Ca2+ (1.5 mmol/L). These results indicate that no hypertension-associated defect in vascular Ca2+ handling exists in mesenteric arteries of the SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Actin Cytoskeleton↗

PubMed1995

Vascular actions of the calcium-regulating hormones.

The vascular actions of the hormones that participate in the regulation of whole animal calcium (Ca2+) homeostasis and related factors are discussed. Parathyroid hormone (PTH) has vasodilator activity that is mediated by a specific cell membrane receptor coupled to adenylate cyclase and thus increases intracellular cAMP and lowers intracellular Ca2+. The peptide may also block voltage-sensitive Ca2+ channels. However, the general consensus is that PTH does not achieve sufficient levels in the serum to modulate vascular reactivity. Parathyroid hormone does, however, share a common receptor and N-terminal amino acid sequence homology with parathyroid hormone-related peptide (PTHrp), which has many of the properties of a locally acting vascular regulator. Exciting actions of the steroid hormone, 1,25(OH)2 vitamin D3, have recently been described which suggest that the hormone is a vascular smooth muscle-differentiating agent and promises to set the stage for learning about the long-term modulatory actions of other steroid hormones. Calcitonin has minimal vascular actions, and although CGRP is not classifiable as a Ca(2+)-regulating hormone, it is a potent vasodilator neurotransmitter. Finally, within the past 2 years there has been a ground swell of activity surrounding the existence of the extracellular Ca2+ receptor that senses changes in interstitial Ca2+. The response of the smooth muscle cell to extracellular Ca2+ is discussed in the context of this receptor.

Animals↗

PubMed1994

A non-cyclo-oxygenase, non-nitric oxide relaxing factor is present in resistance arteries of normotensive but not spontaneously hypertensive rats.

The present experiments tested the hypothesis that decreased production of an endothelium-derived relaxing factor in arteries of hypertensive animals contributes to impaired endothelium-dependent relaxation. Acetylcholine-induced relaxation of freshly isolated spontaneously hypertensive rat (SHR) vessels pre-contracted with norepinephrine was impaired compared with Wistar-Kyoto rats (WKY). 10 microM indomethacin partially normalized the SHR response. Inhibition of nitric oxide synthesis with 100 microM nitro-L-arginine methyl ester or 100 microM NG-monomethyl arginine shifted the acetylcholine relaxation curve to the right, but had no effect on the maximal relaxation in WKY and completely inhibited relaxation of SHR. A similar pattern was observed with methylene blue (0.3 microM). Acetylcholine-induced relaxation of WKY vessels pre-contracted with 5 microM norepinephrine and 100 mM K+ was attenuated 60% compared with vessels pre-contracted with norepinephrine alone, and was completely inhibited by nitro-L-arginine methyl ester; relaxation of SHR vessels was decreased by 50%. Six-hour storage at 37 degrees C significantly attenuated acetylcholine-induced relaxation in both strains; treatment with indomethacin improved the response. Moreover, relaxation of WKY vessels was completely inhibited by nitro-L-arginine methyl ester and NG-monomethyl arginine after the storage period. The absence of L-arginine-induced relaxation and lack of effect of supplementation with L-arginine indicated that the constitutively active NO synthetase was not induced and that L-arginine substrate was limiting. The results indicate that mesenteric resistance arteries of the WKY express a relaxing factor generated by a non-cyclo-oxygenase, non-nitric oxide synthetase pathway that is possibly a hyperpolarizing factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1994

Intracellular Ca2+ and force generation determined in resistance arteries of normotensive and hypertensive rats.

OBJECTIVE: Dysfunctional cellular Ca2+ handling has been proposed to underlie the heightened vascular reactivity observed in the spontaneously hypertensive rat (SHR) model of genetic hypertension. We tested the hypothesis that basal or agonist-induced mobilization of intracellular Ca2+ is elevated in mesenteric resistance arteries of SHR compared with the normotensive Wistar-Kyoto (WKY) rat. DESIGN: A method using fura-2 for the simultaneous measurement of intracellular Ca2+ and isometric force generation in isolated mesenteric resistance arteries was employed to measure agonist-induced changes in Ca2+ and force during activation with 100 mmol/l K+ or 10 mumol/l norepinephrine. Arteries with normalized diameter 220-240 microns from male rats aged 14-15 weeks were examined. RESULTS: No differences were detected between the rat strains in basal Ca2+ concentration or the steady-state concentration of Ca2+ achieved in response to either 100 mmol/l K+ or 10 mumol/l norepinephrine. The relationship between Ca2+ and force during the contractile responses to K+ and norepinephrine was analyzed. No differences between the strains in the level of active stress, normalized to unit intracellular Ca2+, were detected in the steady-state responses to K+ or norepinephrine. CONCLUSIONS: The present results do not support the hypothesis that alterations in either the basal concentration of intracellular Ca2+ or the amount of intracellular Ca2+ mobilized in response to high levels of norepinephrine or K+ are present in resistance arteries of SHR compared with those of WKY rats. Moreover, these findings suggest that elevations in Ca2+ do not contribute to heightened peripheral resistance in SHR.

Animals↗

PubMed1993

Effect of long-term administration of 1,25 (OH)2 vitamin D3 on blood pressure and resistance artery contractility in the spontaneously hypertensive rat.

The effect of long-term daily injection of 1,25 (OH)2 vitamin D3 on blood pressure and contractile force generation by subsequently isolated mesenteric resistance arteries was examined using the spontaneously hypertensive rat (SHR) model of genetic hypertension. Beginning at 6 weeks of age, male SHR were given daily intraperitoneal injections of vehicle, or 1,25 (OH)2 vitamin D3 at 20, 30, or 40 ng/100 g body weight. Body weight and systolic blood pressure were determined weekly. After 9 weeks, serum was prepared for electrolyte analysis and mesenteric resistance arteries were isolated for assessment of contractile function using a wire myograph. Blood pressure became elevated in the rats receiving 20 and 40 ng 1,25 (OH)2 vitamin D3 after 5 weeks and remained elevated in the 40 ng group during the sixth week. Between weeks six to nine, blood pressure continued to rise but was not different among the groups. In addition, during the period between 6 and 9 weeks, there was a decline in the rate of weight gain in rats receiving 30 and 40 ng 1,25 (OH)2 vitamin D3. Serum ionized Ca2+ was significantly elevated in the three groups treated with 1,25 (OH)2 vitamin D3 compared with control. The active stress response of resistance arteries to norepinephrine and arginine vasopressin was significantly elevated in rats that received 30 and 40 ng 1,25 (OH)2 vitamin D3, but no differences in apparent sensitivity to these agonists were detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1993

On the vascular inotropic action of 1,25-(OH)2 vitamin D3.

Previous work from our laboratory showed that injection of 1,25-(OH)2 vitamin D3 (1,25-vitD) into the rat over a 3-day period increases force generating capacity of subsequently isolated resistance arteries. To better understand the mechanism of this vascular inotropic action, we examined the time course of its development and Ca(2+)-associated mechanism of action. Mesenteric resistance arteries were isolated from 12-week-old male spontaneously hypertensive rats (SHR) 6 and 24 h after a single injection and 24 h after three and seven consecutive days of injection of 1,25-vitD (20 ng/100 g) or vehicle. Serum 1,25-vitD was increased nearly threefold at 6 h, but not at later times. Serum total and ionized Ca2+ were not affected at any time point. No changes in contractile force generation were detected at 6 and 24 h, but a significant increase in the active stress response to norepinephrine and arginine vasopressin was observed after both 3 and 7 days of 1,25-vitD treatment. No effect on sensitivity to either agonist was observed at any time point. To determine whether the vascular inotropic effects of 1,25-vitD might translate into changes in blood pressure, 11-week-old male Wistar rats were given daily injections of 1,25-vitD (20 ng/100 g) over a 4-week period, and blood pressure and body weight were measured. While body weight did not differ at any time point in the two groups, systolic blood pressure was elevated in the 1,25-vitD group v control by 7 days, and continued to be elevated over the period of observation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Effect of prostacyclin on platelet intracellular free calcium concentration of hypertensive and normotensive humans.

Platelet intracellular free calcium concentration ([Ca2+]i) has been reported to be increased in essential hypertensive patients (EHT) as compared with normotensive controls (NT). Prostacyclin (PGI2), which influences cellular Ca2+, has been reported to be reduced in EHT. This study tested the hypothesis that the resting level of platelet [Ca2+]i in humans is influenced by PGI2. We also investigated the role of PGI2 in regulating platelet [Ca2+]i of 28 EHT subjects compared to 28 NT controls. Platelet [Ca2+]i was measured using the fluorescent Ca2+ probe fura-2 under control conditions and a 10-min preincubation with PGI2. Simultaneous measurement of platelet cyclic-adenosine 3':5'-monophosphate (cAMP) was performed by radioimmunoassay. The resting level of platelet [Ca2+]i was significantly higher in EHT than in NT (32.7 +/- 1.4 v 28.3 +/- 0.9 nmol/L; P < .01). PGI2 from 30 nM to 1 mumol/L lowered the resting level of platelet [Ca2+]i in a dose-dependent manner (EHT -22.2 +/- 2.4, NT -22.9 +/- 2.3%, 1 mumol/L PGI2); however, no significant difference in platelet [Ca2+]i was observed between NT and EHT. While prostacyclin induced a transient rise in platelet cAMP, the magnitude of PGI2-induced cAMP level was similar between the two groups. These results do not support the hypothesis that endogenous PGI2 activity contributes to the increased level of platelet [Ca2+]i in EHT, although PGI2 incubation lowered the resting level of platelet [Ca2+]i.

Adult↗

PubMed1993

Effect of chronic and subacute parathyroidectomy on blood pressure and resistance artery contractility in the spontaneously hypertensive rat.

OBJECTIVE: Chronic parathyroidectomy (PTX) attenuates blood pressure and increases vascular force generation. The mechanism is not understood. We tested the hypothesis that PTX-induced changes in blood pressure and vessel contractility result from rapid changes in serum parameters induced by PTX, and the hypothesis that the endothelium-derived factors contribute to PTX-induced enhancement of force generation in the spontaneously hypertensive rat (SHR). DESIGN: Chronic PTX or sham surgery was performed on 5-week-old male SHR, and subacute PTX was performed on 13- to 14-week-old SHR. The following experimental parameters were measured 5-6 weeks after chronic and 2 days after subacute PTX: systolic blood pressure, serum Ca2+, 1,25-dihydroxyvitamin D3 (vitD) and mesenteric resistance artery contractility. RESULTS: Chronic PTX significantly reduced blood pressure, body weight and serum Ca2+ compared with sham surgery; subacute PTX reduced only serum Ca2+ and vitD. Compared with sham surgery, the mesenteric resistance artery following chronic PTX showed increased active stress responses to norepinephrine and serotonin that were not associated with changes in free intracellular Ca2+, but were abolished by endothelial denudation. Subacute PTX did not affect the active stress response to norepinephrine or endothelin. Low-dose acetylcholine induced relaxation that was attenuated in the chronic, but not the subacute, PTX subgroup compared with the sham-operated subgroup. High-dose acetylcholine induced contraction that was significantly greater in the chronic, but not subacute, PTX rats than in sham-operated rats. Indomethacin abolished the acetylcholine-induced contraction in all groups, but did not improve the impaired relaxation response of the chronic PTX subgroup. CONCLUSIONS: The PTX-induced decrease in blood pressure and increase in force generation do not result from acute changes initiated by reduction of serum parathyroid hormone, vitD or Ca2+. Moreover, the PTX-induced increase in force generation results from a decrease in the production of a non-cyclo-oxygenase endothelium-dependent relaxing factor.

Animals↗

PubMed1993

Endothelium-dependent relaxation of hypertensive resistance arteries is not impaired under all conditions.

Endothelium-dependent relaxation of mesenteric resistance arteries of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats was studied. Acetylcholine-induced relaxation of SHR vessels precontracted with 10 microM norepinephrine was endothelium dependent and attenuated compared with WKY vessels. The impaired response of SHR vessels was normalized by inhibition of cyclooxygenase with indomethacin. Blockade of nitric oxide synthetase with NG-nitro L-arginine methyl ester (L-NAME) or inhibition of guanylate cyclase with methylene blue attenuated acetylcholine-induced relaxation of norepinephrine-contracted SHR vessels but had no effect on WKY vessels. When vessels were precontracted with 30 nM arginine vasopressin, acetylcholine induced similar degrees of relaxation in both strains. A similar response was detected when lysine vasopressin was used to induce tone. Indomethacin had no effect on relaxation responses of SHR and WKY vessels precontracted with either form of vasopressin. L-NAME and methylene blue partially inhibited acetylcholine-induced relaxation of vasopressin-contracted vessels from both strains. Acetylcholine added at baseline did not induce contraction of vessels from either strain. It is concluded that endothelium-dependent relaxation of SHR resistance arteries is not impaired under all circumstances. Acetylcholine-induced relaxation may be suppressed in SHR resistance arteries when norepinephrine is used to induce contraction as a result of catecholamine-induced production of an endothelium-derived contracting factor. Vasopressin, on the other hand, does not elicit production of this contracting factor and may enhance the vasorelaxant action of acetylcholine in resistance arteries of both strains via actions on endothelial or vascular smooth muscle cells.

Acetylcholine↗

PubMed1993

Changes in extracellular Ca2+ over a physiologic concentration range differentially modulate reactivity of resistance arteries of spontaneously hypertensive and normotensive rats.

Norepinephrine-induced contractile responses of mesenteric resistance arteries of normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats were examined in the presence of 1.25, 1.5, and 2.5 mM extracellular Ca2+. In endothelium-intact WKY segments, the three levels of extracellular Ca2+ had no effect on sensitivity to norepinephrine. However, the response of SHR vessels to low dose norepinephrine was significantly enhanced in the presence of 1.25 and 2.5 mM Ca2+ versus 1.5 mM Ca2+. After endothelial WKY vessels responded like SHR vessels, i.e. sensitivity to norepinephrine was enhanced in 1.25 mM Ca2+ compared with 1.5 mM Ca2+. This response to alterations in extracellular Ca2+ was also observed after blockade of the neuronal amine pump with cocaine. These results indicate that vascular smooth muscle of both SHR and WKY respond to small physiologic changes in extracellular Ca2+ with altered sensitivity to norepinephrine. This effect is independent of the neuronal amine pump. We conclude that the endothelium of the normotensive rat protects against Ca(2+)-induced changes in sensitivity to norepinephrine and this protection is absent in SHR.

Animals↗

PubMed1993

Antiproliferative and endothelium-dependent vasodilator properties of 1,3-dihydro-3-p-chlorophenyl-7-hydroxy-6-methyl-furo-(3,4c) pyridine hydrochloride (cicletanine).

The vasodilator and antiproliferative actions of 1,3-dihydro-3-p-chlorophenyl-7-hydroxy-6-methyl-furo-(3,4c) pyridine hydrochloride (cicletanine) were studied on mesenteric resistance arteries and cultured mesenteric artery myocytes of spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. Cicletanine (20-200 microM) induced relaxation of endothelium-intact mesenteric resistance arteries of SHR and WKY precontracted with norepinephrine. No difference in sensitivity was observed (SHR IC50 = 77 +/- 12 microM vs. 83.3 +/- 7.4 microM for WKY, N.S.). Endothelial denudation of WKY vessels significantly attenuated the relaxing action of cicletanine (IC50 + endo = 83 +/- 7.4 microM vs. IC50 - endo = 135 +/- 9.7 microM; P < .001) and had a similar, but nonsignificant effect on SHR (IC50 + endo = 77 +/- 12 microM vs. IC50 - endo = 117 +/- 14.5 microM; P = .065). Preincubation of endothelium-intact vessels with nitro-L-arginine methyl ester significantly attenuated cicletanine-induced relaxation in WKY, but not SHR vessels; 0.1 mM Ba++ had a similar effect. Preincubation with 3 microM indomethacin was without effect on relaxation of vessels of either strain. Cicletanine (100-1000 microM) inhibited proliferation of cultured superior mesenteric artery muscle cells growing in the presence of either 10% (SHR IC50 = 440 +/- 24 microM vs. 517 +/- 12 microM for WKY; P < .05) or 2% fetal bovine serum. This antiproliferative action was fully reversible, partially inhibited by indomethacin in SHR myocytes and was associated with a decrease in [3H]thymidine uptake in both strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Chronic alcohol consumption lowers blood pressure but enhances vascular contractility in Wistar rats.

OBJECTIVE: To determine the effect of chronic alcohol consumption upon blood pressure, blood pressure reactivity and vascular contractility in Wistar rats. DESIGN: Wistar rats were fed a liquid diet containing 36% ethanol; control rats were pair fed. METHODS: Rats were maintained on diets for 18 weeks. Indirect systolic blood pressure was measured weekly. Catheters were implanted for assessment of direct arterial pressure and blood pressure reactivity to norepinephrine, angiotensin II and ethanol injections. In a subgroup of rats, contractility of isolated mesenteric resistance vessels was measured. RESULTS: In comparison with simultaneously pair-fed controls, ethanol-treated rats developed significantly lower blood pressure within 3 weeks of exposure to alcohol; this continued throughout the study. Despite the reduction in blood pressure, in vitro assessment of vascular contractility in mesenteric resistance vessels indicated that ethanol consumption significantly enhanced vascular contractility to norepinephrine and attenuated the vasodepressive effects of ethanol. Measurement of blood pressure reactivity to infused pressor agents showed no difference between controls and ethanol-treated rats in response to norepinephrine but a significantly attenuated pressor response to angiotensin II was observed in ethanol-treated rats. CONCLUSIONS: The blood pressure results contrast with reports of elevated blood pressure in Wistar rats given ethanol in drinking water. This disparity may be due to nutritional factors. Increased vascular contractility combined with hypotension suggests that cardiovascular regulatory systems offset the direct effects of ethanol upon the vasculature. This view is reinforced by the lack of difference between groups in blood pressure reactivity to norepinephrine. The attenuated angiotensin II responses in the ethanol-treated rats suggests altered levels of circulating angiotensin II in this group.

Alcoholism↗

PubMed1991

1,25 (OH)2 vitamin D3 attenuates the loss of resistance artery contractile function associated with incubation in culture media.

Contractile properties of rat mesenteric resistance arteries were studied immediately after isolation or after 48-hr incubation in culture medium [Dulbecco's modified Eagle's/Ham's F-12 (1:1) with insulin, transferrin and antibiotics]. Incubation in culture medium depressed active stress generating capacity, increased sensitivity to norepinephrine and ablated endothelium-dependent relaxation. The decrease in stress generation results from the loss of a releasable pool of intracellular Ca2+; the enhanced sensitivity is associated with decreased neuronal amine pump function. Addition of 300 pg/ml 1,25 (OH)2 vitamin D3 to the culture medium afforded nearly complete protection against the loss of stress generating capacity and partially preserved endothelial function. It is concluded that 1,25 (OH)2 vitamin D3 partially prevents phenotypic modulation of the vascular myocyte induced by culture conditions.

Acetylcholine↗

PubMed1991

1,25 (OH)2 vitamin D3-induced 45CA uptake in vascular myocytes cultured from spontaneously hypertensive and normotensive rats.

The effect of 1,25 (OH)2 vitamin D3 on basal 45Ca uptake was examined in vascular smooth muscle cells cultured from mesenteric arteries of spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) normotensive rats. Basal uptake of 45Ca was significantly greater in myocytes of WKY than SHR at 5, 10, 30 and 60 min incubation with the isotope. Incubation with 1 ng/ml 1,25 (OH)2 vitamin D3 for 48 hr increased basal 45Ca uptake between 1-10 min in SHR and between 5-10 min in WKY. The dose-response relationship indicated that cells from both strains are equally sensitive to the calciotropic effects of 1,25 (OH)2 vitamin D3 with half-maximal stimulation occurring at approximately 0.3-0.4 ng/ml. In cells of both strains maximal stimulation of 45Ca uptake was achieved only after a 12-24 hr period of incubation with hormone and pretreatment with cycloheximide inhibited 1,25 (OH)2 vitamin D3-enhanced 45Ca uptake. Although 45Ca binding by extracellular matrix material was significantly greater in WKY than SHR, 1,25 (OH)2 vitamin D3 had no effect on the amount of matrix 45Ca binding in either strain. These results suggest that 1,25 (OH)2 vitamin D3 induces an increase in intracellular protein synthesis that results in enhanced 45Ca uptake. The similar responses of the two strains indicate that hypertensive smooth muscle is not more sensitive to 1,25 (OH)2 vitamin D3 and the Ca2+ response is a general property of vascular muscle.

Animals↗