Biomedical subjects

A Hassid

Publications and source records attributed to A Hassid.

At least 19 recordsLinked to original sources

PubMed1991

Clearance receptor-binding atrial natriuretic peptides inhibit mitogenesis and proliferation of rat aortic smooth muscle cells.

The current studies were designed to explore the effects of C-receptor-binding atrial natriuretic peptide analogues on serum-induced mitogenesis in cultured rat aortic smooth muscle cells. To this end, rANF99-126 and a series of truncated (rANF103-126, rANF103-125), ring-deleted (des[Gln116, Ser117, Gly118, Leu119, Gly120]rANF102-121-NH2 (c-ANF) and linear des(Cys105, Cys121)rANF104-126 peptide analogues were used. The latter two peptides have been reported to be selective for the ANF-C receptor. In cells subcultured between passage 3 to 19, rANF99-126, rANF103-126, and rANF103-125 concentration-dependently (0.1-1000 nM) inhibited serum-induced (3H) thymidine incorporation with maximal inhibition observed at 1 microM for each peptide (approximately 40, 31 and 56%) respectively. Furthermore, des[Cys105, Cys121]rANF104-126 inhibited serum-induced (3H)thymidine incorporation concentration-dependently without altering basal or elevated cellular cAMP or cGMP levels. Moreover, the reduction in thymidine incorporation was associated with inhibition of serum-induced clonal cell proliferation. In contrast, c-ANF failed to inhibit serum-induced mitogenesis, yet at a concentration of 100 nM it antagonized the antimitogenic effects of des[Cys105, Cys121]rANF104-126 or rANF99-126 without having any effect on basal or elevated cellular cyclic nucleotide levels. We conclude that the antimitogenic effect of atrial peptides is mediated through interaction with the ANF-C receptor and may be independent of changes in cellular cyclic nucleotide levels.

Animals↗

PubMed1991

Cell density modulates the decrease of cytosolic free Ca2+ induced by atrial natriuretic hormone, S-nitroso-N-acetylpenicillamine and 8-bromo cyclic GMP in cultured rat mesangial cells.

Cyclic GMP-elevating agents, including atrial natriuretic hormone and NO-generating vasodilators, decrease cytosolic free Ca2+ levels in mesangial cells. We have investigated the role of cell density as a modulator of the decrease in cytosolic free Ca2+ induced by the cyclic GMP (cGMP)-elevating vasodilators atrial natriuretic peptide (99-126) [ANP (99-126); 'atriopeptin 28'] and the NO-generating vasodilator S-nitroso-N-acetylpenicillamine (SNAP), in cultured rat mesangial cells. Increasing cell density was significantly correlated with the decrease in cytosolic free Ca2+ induced by ANP (99-126) or SNAP. Moreover, this effect was independent of the cells' proliferative status. ANP (99-126) and SNAP induced greater fold stimulation of cGMP accumulation in high-density cells, but the levels of cGMP elicited by high concentrations of ANP (99-126) or SNAP were similar in high- and low-density cells. 8-Bromo cGMP was more effective in decreasing cytosolic free Ca2+ in high- than in low-density cells, suggesting that the greater effectiveness of ANP (99-126) and SNAP was, in part, due to greater effectiveness of endogenous cGMP in high-density cells. The results document that cell density, but not proliferative status, plays an important role in the modulation of intracellular Ca2+ dynamics in rat mesangial cells by atriopeptins, NO-generating vasodilators and cGMP.

Animals↗

PubMed1991

Nitric oxide decreases cytosolic free calcium in Balb/c 3T3 fibroblasts by a cyclic GMP-independent mechanism.

The purpose of this study was to investigate the effects of NO on cytosolic calcium levels in Balb/c 3T3 fibroblasts that were previously shown to lack soluble guanylate cyclase activity. Authentic NO as well as two NO-generating vasodilators, S-nitroso-N-acetyl-penicillamine and isosorbide dinitrate, decreased cytosolic calcium in these fibroblasts. The effect of NO and S-nitroso-N-acetylpenicillamine was concentration-dependent and, for the most part, reversible. Since S-nitroso-N-acetylpenicillamine did not increase either cGMP or cAMP, NO did not increase cGMP, and 8-bromo-cGMP did not alter cytosolic free calcium, we conclude that NO decreases cytosolic free calcium by a cyclic nucleotide-independent mechanism in Balb/c 3T3 fibroblasts.

1-Methyl-3-isobutylxanthine↗

PubMed1990

Nitric oxide-generating vasodilators inhibit mitogenesis and proliferation of BALB/C 3T3 fibroblasts by a cyclic GMP-independent mechanism.

The purpose of this study was to investigate the effects of nitric oxide-generating vasodilators and 8-bromo-cGMP on serum-induced mitogenesis in BALB/c 3T3 fibroblasts that lack soluble guanylate cyclase activity. Two such vasodilators, S-nitroso-N-acetylpenicillamine and isosorbide dinitrate, decreased the incorporation of (3H)thymidine in these cells dose-dependently whereas 8-bromo-cGMP was ineffective at concentrations of up to 10 mM. Moreover, S-nitroso-N-acetylpenicillamine also inhibited cell proliferation, consistent with the data on (3H)thymidine incorporation. S-nitroso-N-acetylpenicillamine had no effect on cGMP accumulation, confirming previous studies that these cells lack soluble guanylate cyclase activity. Hemoglobin and FeSO4/ascorbate, agents that inhibit the actions of nitric oxide, both decreased S-nitroso-N-acetylpenicillamine-induced antimitogenesis, supporting the view that this effect was related to the generation of nitric oxide. The antimitogenic activity of S-nitroso-N-acetylpenicillamine was unlikely to be the expression of nitric oxide-induced degradation of serum mitogens, as indicated by the decrease of the antimitogenic activity on prolonged preincubation of SNAP in serum-containing medium. We conclude that nitric oxide-generating vasodilators inhibit serum-induced mitogenesis and cell proliferation in BALB/c 3T3 fibroblasts by a cGMP-independent mechanism.

1-Methyl-3-isobutylxanthine↗

PubMed1989

Relationship of GTP-binding proteins, phospholipase C, and PGE2 synthesis in rat glomerular mesangial cells.

We evaluated the role of GTP-binding proteins in the activation of phospholipase C, release of arachidonic acid, and synthesis of prostaglandin (PG) E2 in response to platelet-activating factor (PAF) and angiotensin II (ANG II) in cultured rat mesangial cells. Pretreatment with pertussis toxin (PT) decreased PGE2 formation and arachidonic acid release in response to PAF and ANG II but not that to A 23187. PT pretreatment also inhibited formation of inositol trisphosphate (IP3) in response to ANG II or PAF but did not significantly alter the rise in intracellular calcium detected by fura-2. PT catalyzed ADP ribosylation of two proteins of molecular mass approximately 40 and 41 kDa. Further evidence for involvement of GTP-binding protein in phospholipase C activation was that GTP-gamma S stimulated IP3 generation. Immunoblots with antibodies directed against different inhibitory alpha subunits of GTP-binding proteins showed that the major 40-kDa PT substrate reacted with an antibody directed against a decapeptide of the G protein subunit alpha i2 that is also found in leukocytes. This was further confirmed by Northern blot that showed the existence of mRNA in mesangial cells that hybridized with a cDNA probe for G alpha i2. In addition lesser amounts of mRNA hybridized with a restriction fragment cDNA probe for G alpha i3, which corresponds to the 41-kDa substrate for PT ribosylation. These results show that phospholipase C activation by PAF and ANG II in mesangial cells involves a specific G protein, most likely G alpha i2.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1989

Inhibition of rat mesangial cell mitogenesis by nitric oxide-generating vasodilators.

Recent studies indicate that endothelium-derived relaxing factor (EDRF) may be identical with nitric oxide (NO). The purpose of this study was to investigate the antimitogenic effect of NO-generating drugs in cultured mesangial cells. S-nitroso-N-acetylpenicillamine, sodium nitroprusside, and isosorbide dinitrate, which generate NO, dose dependently inhibited serum-stimulated DNA synthesis. All three drugs also inhibited the rate of cell proliferation, whereas sodium nitroprusside and S-nitroso-N-acetylpenicillamine decreased cell density at confluence. The antimitogenic activity of S-nitroso-N-acetylpenicillamine was labile in culture medium and could be inhibited by hemoglobin, supporting the view that NO, in free or bound form, was the ultimate effector. All three vasodilators increased cellular guanosine 3',5'-cyclic monophosphate (cGMP) levels dose dependently; moreover, 8-bromo-cGMP mimicked the effects of the NO-generating drugs, suggesting that cGMP may be an intracellular mediator of antimitogenesis. The growth-inhibitory effect of S-nitroso-N-acetylpenicillamine was reversible and was not due to cell toxicity as shown by several criteria of cell viability. The results raise the possibility that EDRF/NO may be a modulator of mesangial cell growth in vivo.

Animals↗

PubMed1989

Modulation of Ca by agents affecting voltage-sensitive Ca channels in mesangial cells.

The purpose of this study was to investigate the effects of depolarizing media and of Ca-channel activators and blockers on cytosolic free Ca in cultured rat mesangial cells. Membrane depolarizing media, containing 10-100 mM K+, dose dependently increased cytosolic Ca, and this effect was sustained and reversible. Nifedipine and lanthanum ion inhibited this increase, whereas verapamil was ineffective. A Ca-channel activator, BAY K 8644, dose dependently increased resting Ca levels, and nifedipine inhibited this effect. Moreover, the increase of Ca induced by maximally effective high K+ and BAY K 8644 was additive, suggesting differential mechanisms of action for the two channel activators. Nifedipine and verapamil decreased resting Ca levels by up to 35-40%. The results support the idea that mesangial cells have spontaneously active Ca channels that can be further activated by membrane depolarization or by the Ca-channel activator, BAY K 8644, and inhibited by the Ca-channel blockers, nifedipine or verapamil. Voltage-sensitive Ca channels in mesangial cells may play a role in the regulation of the glomerular filtration rate.

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

PubMed1989

Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells.

Endothelium-derived relaxing factor has been recently identified as nitric oxide. The purpose of this study was to determine if vasodilator drugs that generate nitric oxide inhibit vascular smooth muscle mitogenesis and proliferation in culture. Three chemically dissimilar vasodilators, sodium nitroprusside, S-nitroso-N-acetylpenicillamine and isosorbide dinitrate, dose-dependently inhibited serum-induced thymidine incorporation by rat aortic smooth muscle cells. Moreover, 8-bromo-cGMP mimicked the antimitogenic effect of the nitric oxide-generating drugs. The antimitogenic effect of S-nitroso-N-acetylpenicillamine was inhibited by hemoglobin and potentiated by superoxide dismutase, supporting the view that nitric oxide was the ultimate effector. Sodium nitroprusside and S-nitroso-N-acetylpenicillamine significantly decreased the proliferation of vascular smooth muscle cells. Moreover, the inhibition of mitogenesis and proliferation was shown to be independent of cell damage, as documented by several criteria of cell viability. These results suggest that endogenous nitric oxide may function as a modulator of vascular smooth muscle cell mitogenesis and proliferation, by a cGMP-mediated mechanism.

Animals↗

PubMed1989

Mechanism of atriopeptin-induced decrease of cytosolic free Ca in rat vascular smooth muscle cells: evidence for an intracellular locus of action.

The purpose of this study was to investigate the subcellular mechanism of action of atriopeptins in relation to intracellular Ca dynamics. Atriopeptin 23, an analogue of the circulating hormone, decreased cytosolic free Ca in cultured adherent aortic smooth muscle cells, both in the presence and absence of extracellular Ca. Moreover, the atrial peptide did not alter Ca efflux. Atriopeptin 23 decreased the Ca transient induced by angiotensin II (Ang II), but only at low concentrations of the vasoconstrictor peptide. Similar to atriopeptin 23, S-nitroso-N-acetylpenicillamine, an organic nitrovasodilator that increases cGMP levels in vascular tissues, decreased resting Ca in adherent cells, supporting the notion that cGMP is a mediator of atriopeptin action. The results support the concept that atriopeptin decreases intracellular Ca by enhancing intracellular Ca sequestration and/or inhibiting intracellular Ca release.

Animals↗

PubMed1988

A novel biological effect of atrial natriuretic hormone: inhibition of mesangial cell mitogenesis.

We have investigated the effect of atrial natriuretic hormone on serum-induced mitogenesis in cultured rat mesangial cells. Synthetic peptides, atriopeptin 28 and atriopeptin 24, dose-dependently decreased thymidine incorporation, with a half-maximal effect at approximately 1 nM and a maximal inhibition of approximately 60%. Moreover, atriopeptin 28 significantly decreased the clonal proliferation of mesangial cells. Atriopeptin 28 also decreased resting cytosolic Ca but had no effect on the increase induced by serum, relative to the lower baseline established by atriopeptin 28. Nevertheless, the overall effect of atriopeptin 28 on Ca was to attenuate the serum-induced increase, relative to the original resting level. These results therefore provide evidence for a novel biological effect of atrial natriuretic hormone and suggest that the antimitogenic effect may be mediated by atriopeptin-induced alterations of intracellular Ca dynamics. We speculate that atrial natriuretic hormone may be a modulator of mesangial cell mitogenesis in vivo.

Animals↗

PubMed1988

Mediation of augmented monocyte adhesiveness by thromboxane.

We examined the potential contribution of thromboxanes in human monocyte adherence to plastic. Monocyte adherence to plastic could be augmented by various stimuli including lipopolysaccharide, chemotactic peptide, and supernates of antigen-stimulated lymphocytes. Increments in monocyte adhesiveness were suppressed by inhibition of cyclooxygenase, thromboxane synthetase, or by antiserum to thromboxane B2. Neither prostaglandin E2 or F2 alpha significantly affected baseline or lipopolysaccharide-stimulated monocyte adherence. Additional experiments confirmed incremental production of thromboxane B2 by monocytes after incubation with lipopolysaccharide. Thromboxane B2 itself did not stimulate monocyte adhesiveness. These data demonstrate that monocytes release thromboxane A2 following stimulation and suggest that thromboxane A2 may play a significant role in monocyte-substrate attachment.

Carbazoles↗

PubMed1987

Effects of bradykinin and angiotensin II on intracellular Ca2+ dynamics in endothelial cells.

The purpose of this study was to investigate the effects of angiotensin II and bradykinin on intracellular Ca2+ dynamics in cultured endothelial cells. We used the "second-generation" fluorescent Ca2+ indicator fura-2, in conjunction with dual-wavelength fluorescence spectroscopy, in cultured adherent pulmonary arterial endothelial cells. Angiotensin II (up to 2 microM) had no consistent effect on intracellular Ca2+ levels. In contrast, bradykinin (10 nM) elicited a transient increase of cytosolic free Ca2+, from the resting value of 37 +/- 5 to 647 +/- 123 nM, followed by a decline to a steady-state value of 113 +/- 14 nM, which was significantly higher than the resting Ca2+ levels. Bradykinin's Ca-stimulatory effect was dose dependent, having a half-maximally effective concentration of approximately 1 nM and a maximally effective concentration of 10 nM. A B1-receptor agonist, Des-Arg9-bradykinin, was much less effective than bradykinin as modulator of cytosolic Ca2+. Moreover, a B1-receptor antagonist, Des-Arg9, [Leu8]-bradykinin, did not significantly affect the increase of cytosolic Ca2+ elicited by bradykinin. On the other hand, the bradykinin-elicited increase of Ca2+ was almost completely inhibited by a novel B2-receptor antagonist, D-Arg-[Hyp3, Thi5,8, D-Phe7]-bradykinin. Bradykinin increased cytosolic free Ca2+ levels in cells maintained in Ca2+-deficient extracellular medium, suggesting that the peptide mobilized Ca2+ from intracellular stores. However, the absence of extra-cellular Ca2+ resulted in an 80-90% attenuation of the transient Ca2+ response, whereas the posttransient steady-state response was completely absent. These findings are consistent with the notion that the bradykinin-elicited transient Ca2+ response is dependent on both extra- and intracellular Ca2+ and that the posttransient steady-state response is entirely dependent on extracellular Ca2+. Endothelial cells were responsive to a second dose of bradykinin after a 10-min interim period of incubation in the absence of the peptide hormone. The absence of extracellular Ca2+ during the interim period, or the pretreatment of cells with ionomycin in the absence of extracellular Ca2+, prevented the response of the cells to a second dose of bradykinin. Bradykinin- or ionomycin-desensitized cells could be resensitized by a brief incubation period in Ca2+-replete medium. The results are consistent with the notions that cellular resensitization requires the replenishment of intracellular Ca2+ and that bradykinin, but not angiotensin II, modulates intracellular Ca2+ dynamics in endothelial cells by interacting with a B2-type receptor.

Angiotensin II↗

PubMed1987

Atriopeptins decrease resting and hormone-elevated cytosolic Ca in cultured mesangial cells.

The purpose of this work was to investigate the effects of atrial peptides on the cytosolic Ca levels of cultured, adherent, mesangial cells. Resting Ca levels, measured by the use of fura-2, were dose-dependently decreased by up to 30%, by atriopeptin 23. The half-maximal effect was elicited by approximately 30 pM atriopeptin-23. Atriopeptin 21 also decreased resting Ca levels by up to 30%, but this peptide was approximately 30-fold less potent than atriopeptin 23. Atriopeptin 23 (100 nM) inhibited both the Ca transient and the peak Ca value elicited by 1 nM vasopressin, but the atrial peptide had no significant effect on the Ca transient elicited by higher vasopressin concentrations. At concentrations lower than 100 nM, atriopeptin 23 had no effect on the vasopressin-induced Ca transient. Atriopeptin 23 also decreased the Ca transient and the peak Ca value elicited by 100 nM angiotensin II. Similar to vasopressin, the angiotensin II-induced Ca transient was inhibited by 100 nM but not lower concentrations of atriopeptin 23. In contrast to the effect of atriopeptin 23, atriopeptin 21 (100 nM) had no effect on the Ca transient elicited by vasopressin. These results demonstrate that atriopeptins function as modulators of resting and, under certain conditions, of hormone-increased Ca levels in cultured mesangial cells.

Angiotensin II↗

PubMed1987

Neuropeptide Y enhances the release of luteinizing hormone (LH) induced by LH-releasing hormone.

Depending upon the steroid hormonal milieu, centrally administered neuropeptide Y (NPY) exerts differential effects on the release of LH. Ovarian hormones also effect the concentrations of NPY in hypothalamic nuclei, and some of the changes are similar to those caused by LHRH. The present studies tested whether NPY acts directly on the pituitary gland, either alone or in combination with LHRH, to modify LH secretion. Hemipituitary fragments obtained from ovariectomized rats were incubated in medium 199, and the in vitro effects on LH release of LHRH, NPY, or the two peptides together were assessed. As expected, LHRH (10(-9)-10(-7) M) produced a dose-dependent release of LH, whereas NPY alone had a lesser stimulatory effect at concentrations of 10(-7) or 10(-6) M. On the other hand, 10(-6) M NPY significantly enhanced LH release in response to 10(-9) M LHRH. A potentiation by NPY of the LHRH-induced LH response was observed in an anterior pituitary cell culture system. Cells from the pituitaries of ovariectomized rats were dispersed and cultured for 3 days in medium 199 with BSA, gentamicin, horse serum, and fetal calf serum. During a 3-h incubation, NPY alone (10(-9)-10(-7) M) failed to affect LH release, but significantly potentiated the release induced by 10(-9) or 10(-8) M LHRH. These findings are in accord with the hypothesis that hypothalamic NPY neurons may participate in the regulation of LH secretion in the rat and indicate that one of the mechanisms of its action may be to increase the pituitary LH response to LHRH.

Animals↗

PubMed1986

Relationship between cellular calcium and prostaglandin synthesis in cultured vascular smooth muscle cells.

We have investigated the effects of extracellular and intracellular Ca deficits and of pharmacologic agents thought to inhibit Ca influx or intracellular Ca mobilization on vasopressin-evoked changes of cytosolic Ca2+ levels and PG synthesis in cultured rat mesenteric arterial vascular smooth muscle cells. Vasopressin rapidly increased cytosolic Ca2+ as well as PG synthesis. The increase of cytosolic Ca2+ and the rate of PG synthesis were both maximal within the first minute of incubation. An extracellular Ca deficit of short duration partially inhibited both vasopressin-evoked PG synthesis and the increase of cytosolic Ca2+ by 40 to 60%. Two procedures which deplete cells of some of their intracellular Ca, namely a 30 min incubation in EGTA-supplemented, Ca-lacking media, or a 1 min incubation with ionophore A23187 in Ca-deficient media, decreased PG synthesis by 65% to 100%. The addition of extracellular Ca to Ca-depleted cells restored the ability of vasopressin to stimulate PG synthesis. Two Ca channel antagonists, nifedipine or cinnarizine, had no effect on either vasopressin-evoked PG synthesis or increased cytosolic Ca2+, whereas TMB-8 (10 microM), a putative inhibitor of intracellular Ca mobilization, decreased PG synthesis by 75% by inhibiting acylhydrolase as well as cyclo-oxygenase activities, but had no effect on basal or vasopressin-evoked increase of cytosolic Ca2+, documenting that its inhibitory effect was not a consequence of decreased cytosolic Ca2+. These results demonstrate that decreased cellular Ca levels are associated with decreased cytosolic Ca2+ levels and PG synthesis, and support the hypothesis of a link between, on the one hand, cellular Ca and/or cytosolic Ca2+ and on the other hand, PG synthesis.

Animals↗

PubMed1986

Atriopeptin II decreases cytosolic free Ca in cultured vascular smooth muscle cells.

We have examined the hypothesis that atriopeptin II decreases cytosolic free Ca concentrations in cultured aortic smooth muscle cells. Ca levels were measured, using the Ca indicator fura-2, by dual wavelength fluorescence spectroscopy, in superfused primary cultures of smooth muscle cells. Basal Ca values were between 40 and 100 nM. Angiotensin II (10 nM) elicited a transient threefold increase in Ca, followed by return to a sustained Ca level that was 30% higher than the original basal values. Atriopeptin II dose-dependently decreased basal Ca concentrations by 10-40%. Atriopeptin II did not have a significant effect on the transient Ca response elicited by 10 nM angiotensin II, but the atrial peptide dose-dependently decreased the sustained increase that followed the transient response. Atriopeptin II also decreased cytosolic Ca levels that were elevated by 50 mM KCl. These results support the hypothesis that atriopeptins relax vascular smooth muscle by decreasing basal and vasoconstrictor-elevated cytosolic free Ca levels and that these peptides may function as endogenous antagonists of Ca-mediated processes.

Angiotensin II↗

PubMed1986

Effects of vasoactive peptides on cytosolic calcium in cultured mesangial cells.

We have used the "second generation" Ca indicator, fura-2, to measure cytosolic free Ca concentrations in superfused cultures of adherent primary renal mesangial cells. The basal cytosolic free Ca concentration in these cells was found to be 93 +/- 5 nM (n = 35). The Ca ionophore ionomycin (0.1 microM) increased cytosolic Ca levels to a peak value of fourfold above basal, followed by a decline to a steadily maintained concentration of twofold above basal. Two vasoactive peptide hormones, arginine vasopressin and angiotensin II, at maximally effective concentrations, transiently increased cytosolic free Ca levels to peak values of three- and sixfold, respectively, above basal levels. The angiotensin II-evoked increase declined to near basal values before rising again to a value of 1.5- to 2-fold above basal. Cells treated with vasopressin did not have a significant secondary increase of Ca above a small, time-dependent, spontaneous increase. Mesangial cells demonstrated tachyphylaxis to both peptides. However, cross-tachyphylaxis was not observed. Treatment of cells with angiotensin II in ethyleneglycol-bis-(beta-aminoethylether)-N,N'-tetraacetic acid-supplemented Ca-deficient medium, or with the Ca channel blockers nifedipine or verapamil, did not eliminate the transient phase of cytosolic Ca metabolism. In contrast, the Ca channel blockers completely inhibited the second sustained Ca response to angiotensin II. These results indicate that angiotensin II and vasopressin mobilize intracellular Ca in cultured adherent mesangial cells. Angiotensin II, but not vasopressin, also appears to increase cytosolic Ca by influx of extracellular Ca through specific channels.

Angiotensin II↗

PubMed1986

Functional properties of glomerular cells in culture.

With the development of techniques to isolate and propagate homogeneous cultures of glomerular cell types, numerous investigations have been initiated to study the functional characteristics of cultured glomerular cells. Since much of the work to date has been performed on glomerular mesangial cells, a good deal of this discussion will be about this cell type. Glomerular mesangial cells together with the surrounding matrix material form the glomerular mesangium. These cells contain contractile microfilaments as well as receptors for vasoconstrictor substances such as angiotensin II. Therefore, one proposed function of this cell type is the regulation of glomerular perfusion and filtration by contraction. Cultured mesangial cells contract in response to angiotensin II and arginine vasopressin and, in addition, produce prostaglandins which may function to regulate contraction. In this article, we will review the evidence that has accumulated concerning the contractile nature of mesangial cells. Since prostaglandins may influence mesangial cell contraction, the prostaglandin synthetic capabilities of glomerular epithelial and mesangial cells will be discussed. We will conclude by discussing how glomerular cell culture can be used to study the pathobiology of certain glomerular diseases.

Angiotensin II↗