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Gabor Kaley

Publications and source records attributed to Gabor Kaley.

34 records · Page 2Linked to original sources
PubMed2004

Premature death and age-related cardiac dysfunction in male eNOS-knockout mice.

The aims of our study were to determine mortality, and age- and genotype-related cardiac phenotype in endothelial nitric oxide synthase (NOS) knockout (-/-) and wild-type (+/+) mice. Male and female (-/-) and male and female (+/+) conscious mice were studied at different ages by echocardiography and tail-cuff blood pressure (BP) measurement. Only 50% male (-/-) mice lived longer than 21 months whereas 89% (+/+) mice were still alive after 24 months (P < 0.005). There was little mortality in female mice of either genotype. Both (-/-) and (+/+) male mice have normal cardiac dimensions and function at 5.5 months. However, (-/-) mice developed cardiac dilation and dysfunction at 21 months as evidenced by a significant increase (P < 0.05) in left ventricular (LV) end-diastolic diameter from 2.69 +/- 0.13 to 3.13 +/- 0.09 mm, LV end-systolic diameter from 1.28 +/- 0.11 to 1.86 +/- 0.12 mm, LV end-diastolic cavity volume from 21 +/- 2.8 to 31 +/- 2.5 microl and LV mass from 19 +/- 2.5 to 27 +/- 1.9 mg/10 g and a significant decrease (P < 0.05) in ejection fraction (from 65 +/- 3.3% to 41 +/- 4.6%), shortening fraction (from 53 +/- 2.2% to 41 +/- 3.4%), LV posterior wall thickening (from 27 +/- 2% to 12 +/- 4%) and septum thickening (from 27 +/- 2% to 12 +/- 4%) compared with those at 5.5 months. There was a clear increase in cardiac weight and cardiac dilation by hematoxylin and eosin in male (-/-) mice at 21 months. BP in male (-/-) mice fell with the cardiac dysfunction, whereas female (-/-) mice were hypertensive even at 21 months. The level of mRNA for neuronal NOS and inducible NOS was greater in all females compared to males. These results indicate that male (-/-) mice have a significantly shorter lifespan than (+/+) or female mice, and male (-/-) mice develop cardiac dysfunction with age.

Aging↗
PubMed2004

Nitric oxide and prostaglandins modulate pressure-induced myogenic responses of intramural coronary arterioles.

The myogenic response, an active constriction and dilation of vessels to changes in intravascular pressure, can play an important role in the regulation of coronary blood flow. The characteristics of the myogenic response and its modulation by endothelium-derived factors are organ and location specific and have not been studied extensively in intramural coronary arterioles. Thus, distal intramural branches (approximately 100 and approximately 170 microm active and passive diameter, respectively) of the left anterior descending coronary artery of rats were isolated and cannulated. Step increases in intraluminal pressure from 0 to 40 mm Hg elicited increases in diameter, whereas further increases in pressure from 50 to 150 mm Hg resulted in constrictions. In control, the pressure-induced myogenic tone of coronary arterioles was 67.3 +/- 2.7% of passive diameter (PD, obtained in Ca2+-free solution) at 60 mm Hg. Nomega-nitro-L-arginine (L-NNA, 10(-5) M), an inhibitor of nitric oxide synthase, reduced the initial arteriolar diameter (by 44.8 +/- 5.1 microm at 2 mm Hg, P < 0.05) and significantly mitigated increases in diameter to lower pressures and constrictions to higher pressures (41.1 +/- 5.6% of PD at 60 mm Hg). Administration of adenosine restored the initial diameter in the presence of l-NNA, but the increase in diameter to lower pressures and the decrease in diameter to higher pressures observed under control conditions remained greatly inhibited. Inhibition of prostaglandin synthesis, or PGH2/TxA2 receptors significantly reduced the constrictions to higher pressures as compared with control (indomethacin: from 57.9 +/- 4.8% of PD to 67.0 +/- 4.7% of PD at 150 mm Hg). Thus, because in isolated intramural coronary arterioles of rats a negative slope for the pressure-diameter curve develops only in the presence of nitric oxide and constrictor prostaglandins, they seem to be essential for the normal development of the myogenic response.

Adenosine↗
PubMed2003

Estrogen elicits cytochrome P450--mediated flow-induced dilation of arterioles in NO deficiency: role of PI3K-Akt phosphorylation in genomic regulation.

This study investigated the mechanisms responsible for the estrogen-dependent, cytochrome P450 (CYP)-mediated dilator responses to shear stress in arterioles of NO-deficient female rats and mice. Flow-induced dilation (FID) was assessed in isolated arterioles from N(G)-nitro-L-arginine methyl ester (L-NAME)-treated male and ovariectomized female rats before and after overnight incubation with 17beta-estradiol (17beta-E2, 10(-9) mol/L). In control conditions, prostaglandins (PGs) mediated FID, because indomethacin (INDO) abolished the responses. After incubation of the vessels with 17beta-E2, the basal tone of arterioles was significantly reduced and FID was augmented. INDO did not affect the dilation of the vessels incubated with 17beta-E2. Dilations of these vessels, however, were eliminated by PPOH and miconazole, inhibitors of CYP/epoxygenase. Simultaneous incubation of the vessels with 17beta-E2 plus ICI, 182,780, an estrogen receptor antagonist, or wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K) phosphorylation or the transcriptional inhibitor DRB, prevented the reduced arteriolar tone and the enhanced CYP-mediated FID caused by incubation of vessels with 17beta-E2. Western blot analysis indicated a significantly increased phospho-Akt level in arterioles incubated with 17beta-E2 compared with those without 17beta-E2. The enhanced phospho-Akt in response to 17beta-E2 was localized, by immunohistochemistry, to arteriolar endothelial cells. Moreover, GC-MS analysis indicated a significantly increased production of epoxyeicosatrienoic acids, vasodilator metabolites of CYP/epoxygenase, in arterioles incubated with 17beta-E2, a response that was prevented by ICI 182780 and wortmannin, respectively. Thus, estrogen, via a receptor-dependent, PI3K/Akt-mediated pathway, transcriptionally upregulates CYP activity, leading to an enhanced arteriolar response to shear stress.

Androstadienes↗
PubMed2003

Coronary microvascular endothelial stunning after acute pressure overload in the conscious dog is caused by oxidant processes: the role of angiotensin II type 1 receptor and NAD(P)H oxidase.

BACKGROUND: Few studies have examined the effect of acute pressure overload on endothelial function in the coronary microcirculation. METHODS AND RESULTS: In instrumented conscious dogs with heart rate held constant, veratrine caused a cholinergic nitric oxide (NO)-dependent increase in coronary blood flow by 23+/-3 mL/min (Bezold-Jarisch reflex). Ten minutes after release of constriction of the ascending aorta to increase left ventricular (LV) systolic pressure to 214+/-5 mm Hg for 30 minutes, the veratrine-induced increase in coronary blood flow (7+/-1 mL/min) was reduced by 66% and remained depressed for 2 hours (ie, endothelial stunning [ES]). Nitrite production from isolated coronary microvessels during ES was not different from normal. Ascorbic acid (AA), losartan, or apocynin prevented ES. Myocardial oxygen consumption (MVO2) of LV tissue was measured in vitro in response to bradykinin with preincubation of angiotensin II for 30 minutes. Bradykinin (10(-4) mol/L)-induced reduction in MVO2 was reversed in a concentration-dependent manner by angiotensin II (38+/-1% versus 19+/-2% at 10(-8) mol/L) and restored by coincubation of AA (37+/-2%), tempol (33+/-2%), losartan (34+/-2%), or apocynin (36+/-1%). Exogenous NO-induced reduction in MVO2 was not altered by angiotensin II. Angiotensin II increased lucigenin-detectable superoxide anion in LV tissue in a manner that was inhibited by bradykinin, AA, tempol, losartan, or apocynin. CONCLUSIONS: Endothelial stunning is caused by oxidant processes inhibited by ascorbate, and the activation of NAD(P)H oxidase by increased angiotensin II plays an important role in this process.

Acetophenones↗
PubMed2003

PPARgamma activation, by reducing oxidative stress, increases NO bioavailability in coronary arterioles of mice with Type 2 diabetes.

We tested the hypothesis that short-term treatment of mice with Type 2 diabetes mellitus (DM) with rosiglitazone (ROSI), an agonist of peroxisome proliferator-activated receptor-gamma, ameliorates the impaired coronary arteriolar dilation by reducing oxidative stress via a mechanism unrelated to its effect on hyperglycemia and hyperinsulinemia. Control and Type 2 DM (db/db) mice were treated with ROSI (3 mg x kg(-1) x day(-1)) for 7 days, which did not significantly affect their serum concentration of glucose and insulin. Compared with controls, in db/db mice serum levels of 8-isoprostane and dihydroethydine-detectable superoxide production in carotid arteries were significantly elevated and were reduced by ROSI treatment. In coronary arterioles (diameter, approximately 80 microm) isolated from db/db mice, the reduced dilations to ACh, the nitric oxide (NO) donor NONOate, and increases in flow were significantly augmented either by in vitro administration of apocynin, an inhibitor of NAD(P)H-oxidase, or by in vivo ROSI treatment, responses that were then significantly reduced by the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester. In aortas of db/db mice, activity of SOD and catalase was reduced, whereas NAD(P)H oxidase activity was enhanced. ROSI treatment enhanced catalase and reduced NAD(P)H oxidase activity but did not affect the activity of SOD. These findings suggest that ROSI treatment enhances NO mediation of coronary arteriolar dilations due to the reduction of vascular NAD(P)H oxidase-derived superoxide production and enhancement of catalase activity. Thus, in addition to the previously revealed beneficial metabolic effects, the antioxidant action of rosiglitazone may protect coronary arteriolar function in Type 2 DM.

Acetylcholine↗
PubMed2003

Superoxide-NO interaction decreases flow- and agonist-induced dilations of coronary arterioles in Type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2-DM) markedly increases the incidence of ischemic heart disease (IHD) and, consequently, mortality. However, the underlying mechanisms leading to IHD in T2-DM are not completely understood. We hypothesized that in T2-DM the regulation of coronary microvascular resistance by local mechanisms is altered. Thus, in coronary arterioles (diameter: approximately 80 microm) isolated from male mice with T2-DM (C57BL/KsJ-db/db) and control littermates, responses to changes in intraluminal pressure, flow, and agonists with known mechanisms of action were studied. Increases in pressure (from 20 to 120 mmHg) resulted in similar myogenic responses of coronary arterioles of control and db/db mice, whereas dilations in response to cumulative concentrations of ACh and the nitric oxide (NO) donor NONOate were significantly decreased compared with those of control vessels. On the other hand, responses to adenosine were not different between vessels of control and db/db mice. Increases in flow (0-20 microl/min) resulted in dilations of control vessels (maximum: 38 +/- 4%) that were inhibited by the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME). In contrast, arterioles of db/db mice exhibited greatly reduced dilations to flow (maximum: 4 +/- 6%) that were unaffected by L-NAME. In carotid arteries of db/db mice, superoxide dismutase (SOD)-sensitive, enhanced superoxide production was detected by dihydroethydine staining and lucigenin enhanced chemiluminescence. Correspondingly, intraluminal administration of SOD significantly augmented flow-, ACh-, and NONOate-induced dilations of diabetic arterioles, and then flow- and ACh-induced responses could be inhibited by L-NAME. Collectively, these findings suggest that in T2-DM, due to an enhanced superoxide production, NO mediation of agonist- and flow-induced dilations of coronary arterioles is reduced. This alteration in the regulation of coronary microvascular resistance may contribute to the development of IHD in T2-DM.

Acetylcholine↗
PubMed2003

Aging-induced proinflammatory shift in cytokine expression profile in coronary arteries.

The phenotypic and functional changes of coronary arteries with aging promote ischemic heart disease. We hypothesized that these alterations reflect an aging-induced proinflammatory shift in vascular regulatory mechanisms. Thus, in isolated coronary arteries of young (3-month-old) and aged (25-month-old) male Fischer 344 rats the expression of 96 cytokines, chemokines, and their receptors were screened by a cDNA-based microarray technique. In aged vessels expressions of tumor necrosis factor (TNF)-alpha (3.3x), interleukin (IL)-1beta (3.0x), IL-6 (2.9x), IL-6Ralpha (2.8x) and IL-17 (6.1x) genes were significantly increased over young vessels. Quantitative reverse transcriptase-polymerase chain reaction confirmed these results. Western blotting demonstrated that protein expressions of TNF-alpha, IL-1beta, IL-6, and IL-17 were also significantly increased in vessels of aged rats compared with those of young rats. Immunofluorescent double labeling showed that in aged vessels IL-1beta and IL-6 are predominantly localized in the endothelium, whereas TNF-alpha and IL-17 are localized in smooth muscle. Thus, a proinflammatory shift in the profile of vascular cytokine expression may contribute to the aging-induced phenotypic changes in coronary arteries, promoting the development of ischemic heart disease in the elderly.

Aged↗
PubMed2003

Increased superoxide production in coronary arteries in hyperhomocysteinemia: role of tumor necrosis factor-alpha, NAD(P)H oxidase, and inducible nitric oxide synthase.

OBJECTIVE: In coronary arteries, hyperhomocysteinemia (HHcy, a known risk factor for coronary heart disease) impairs flow-induced dilations, which can be reversed by superoxide dismutase (SOD). To evidence increased O2*- generation and elucidate its source, we characterized changes in activity (lucigenin chemiluminescence, hydroethidine staining) and expression of arterial pro- and antioxidant systems (Western blotting, immunohistochemistry, cDNA microarray, reverse-transcription polymerase chain reaction) in the coronary arteries of rats by using methionine diet-induced HHcy. METHODS AND RESULTS: The increased generation of O2*- by HHcy coronary arteries was inhibited by SOD, diphenyleneiodonium, apocynin, and apocynin plus amino guanidine but was unaffected by allopurinol and rotenone. Also, diphenyleneiodonium-sensitive NADPH-driven O2*- generation was increased in HHcy vessels. In HHcy arteries expression of the smooth muscle-confined NAD(P)H oxidase subunit nox1 and that of iNOS was increased. Expression of p67phox, p22phox, and p47phox subunits and that of endothelial nitric oxide synthase, Cu,Zn-SOD, Mn-SOD, extracellular SOD (mRNA), and xanthine oxidase was unchanged. Microarray analysis showed increased expression of tumor necrosis factor (TNF)-alpha (confirmed by reverse-transcription polymerase chain reaction, Western blotting, and immunohistochemistry) that was localized in smooth muscle. In vitro incubation (18 hours) of HHcy arteries with anti-TNF-alpha antibody decreased O2*- production, whereas incubation of control vessels with TNF-alpha increased O2*- generation and nox1 expression. CONCLUSIONS: In coronary arteries, HHcy increases TNF-alpha expression, which enhances oxidative stress through upregulating a nox1-based NAD(P)H oxidase and inducible nitric oxide synthase. Thus, TNF-alpha induces a proinflammatory vascular phenotype in HHcy that potentially contributes to the development of coronary atherosclerosis.

Animals↗
PubMed2003

Myogenic responses of isolated adipose tissue arterioles.

Previous in vivo studies indicate that vascular autoregulation does take place in adipose tissue. We tested the hypothesis that adipose tissue arterioles can develop a myogenic response to increases in transmural pressure. Arterioles, isolated from the inguinal fat pad of male Wistar rats, were placed in a microvessel chamber containing a Kreb's bicarbonate-buffered solution (pH 7.4) gassed with 10% O2 (5% CO2; 85% N2). Vessels were cannulated and pressurized to 100 mm Hg and studied under no-flow conditions. Control diameters were obtained at 100 mm Hg. Changes in arteriolar diameter were observed and measured by television microscopy and video caliper. Diameters, in response to 20 mm Hg step increases in transmural pressure, were measured before and after removal either of extracellular calcium or of the endothelium, and administration of indomethacin (10(-5) M) or L-NAME (3 x 10(-4) M). Removal of calcium resulted in an increase in control diameter of 81% and completely eliminated the myogenic response. In contrast, administration of indomethacin increased control diameter by 13%. L-NAME significantly enhanced the myogenic response; however, neither endothelium removal nor indomethacin had any significant effect. These results indicate that adipose tissue arterioles are capable of eliciting a myogenic response that could contribute to the regulation of blood flow in vivo. Furthermore, it appears that calcium is essential for the myogenic response and that nitric oxide significantly contributes to the modulation of baseline myogenic tone, as well as the myogenic response.

Adipose Tissue↗
PubMed2002

Norepinephrine elicits beta2-receptor-mediated dilation of isolated human coronary arterioles.

BACKGROUND: The exact role of adrenoceptors in norepinephrine (NE)-mediated regulation of the human coronary circulation has yet to be elucidated. Thus, the goals of this study were to characterize the adrenoceptors involved in the responses to NE in isolated human coronary arterioles and small arteries. METHODS AND RESULTS: Arterioles (n=39) and small arteries from the left ventricle of explanted human hearts were isolated and cannulated. Vessels from the hearts of 21 patients were studied: 15 males and 6 females, aged 0.5 to 63 years. Nineteen patients were considered to be New York Heart Association class 4. All hearts exhibited hypertrophy (190+/-20%). The passive diameter of arterioles was 167+/-8 microm (range 97 to 323 microm). NE (10(-7) to 3x10(- 7) mol/L) elicited concentration-dependent dilations (47+/-4 microm) that were unaffected by endothelium removal, N(omega)-nitro-L-arginine (10(- 4) mol/L, an NO synthase inhibitor), or practolol (10(-6) mol/L, a beta1-receptor blocker). However, administration of propranolol (10(-5) mol/L, a combined beta1- and beta2-blocker) or butoxamine (10(-6) mol/L, a beta2-receptor blocker) completely eliminated the NE-induced dilation. Constrictions to NE (2 of 39 vessels) were inhibited by prazosin (10(-6) mol/L, an alpha1-receptor blocker). Methoxamine (10(-9) to 10(-5) mol/L, an alpha1-agonist) had no effect, whereas U44619, a thromboxane mimetic, elicited dose-dependent constriction of vessels. CONCLUSIONS: Our data indicate that isolated human coronary arterioles and small arteries dilate to NE via beta2-receptors on smooth muscle. These findings are important to our understanding of the mechanisms action of NE in the human coronary circulation.

Adolescent↗
PubMed2002

Aging-induced phenotypic changes and oxidative stress impair coronary arteriolar function.

We aimed to elucidate the possible role of phenotypic alterations and oxidative stress in age-related endothelial dysfunction of coronary arterioles. Arterioles were isolated from the hearts of young adult (Y, 14 weeks) and aged (A, 80 weeks) male Sprague-Dawley rats. For videomicroscopy, pressure-induced tone of Y and A arterioles and their passive diameter did not differ significantly. In A, arterioles L-NAME (a NO synthase blocker)-sensitive flow-induced dilations were significantly impaired (Y: 41+/-8% versus A: 3+/-2%), which could be augmented by superoxide dismutase (SOD) or Tiron (but not L-arginine or the TXA(2) receptor antagonist SQ29,548). For lucigenin chemiluminescence, O(2)(.-) generation was significantly greater in A than Y vessels and could be inhibited with SOD and diphenyliodonium. NADH-driven O(2)(.-) generation was also greater in A vessels. Both endothelial and smooth muscle cells of A vessels produced O(2)(.-) (shown with ethidium bromide fluorescence). For Western blotting, expression of eNOS and COX-1 was decreased in A compared with Y arterioles, whereas expressions of COX-2, Cu/Zn-SOD, Mn-SOD, xanthine oxidase, and the NAD(P)H oxidase subunits p47(phox), p67(phox), Mox-1, and p22(phox) did not differ. Aged arterioles showed an increased expression of iNOS, confined to the endothelium. Decreased eNOS mRNA and increased iNOS mRNA expression in A vessels was shown by quantitative RT-PCR. In vivo formation of peroxynitrite was evidenced by Western blotting, and immunohistochemistry showing increased 3-nitrotyrosine content in A vessels. Thus, aging induces changes in the phenotype of coronary arterioles that could contribute to the development of oxidative stress, which impairs NO-mediated dilations.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
PubMed2002

Decreased arteriolar sensitivity to shear stress in adult rats is reversed by chronic exercise activity.

OBJECTIVE: We tested the hypothesis that the decline in endothelium-dependent arteriolar dilation in adult rats is reversed by chronic exercise activity. METHODS: Rats were divided into young (8-10 weeks)-sedentary (SED(Y)), adult (29-32 weeks)-sedentary (SED(A)), and adult-exercised (EX(A), treadmill exercise for 18-20 weeks) groups. Responses of isolated arterioles ( approximately 50 microm at 80 mm Hg) of gracilis muscle were assessed to increases in perfusate flow and vasoactive agents. RESULTS: With no differences in basal tone, maximal flow-induced dilations were not different between arterioles of SED(Y) and SED(A) rats (71 +/- 2 and 72 +/- 2% of passive diameter, respectively), yet the sensitivity of arterioles to shear stress (WSS(50)) was significantly less in SED(A) than in SED(Y) rats (35 +/- 4 vs. 23 +/- 3 dyne/cm(2), respectively). In vessels of EX(A) rats, maximal flow-induced dilation was significantly augmented (88 +/- 2% of passive diameter) and WSS(50) (15 +/- 1 dyn/cm(2)) was significantly reduced. Dilation to acetylcholine was enhanced in arterioles of EX(A), whereas dilation to sodium nitroprusside was not different in vessels of the three groups. CONCLUSION: Chronic exercise activity reverses age related reduction in sensitivity of arterioles to increases in wall shear stress.

Acetylcholine↗
PubMed2002

Neuronal NOS-dependent dilation to flow in coronary arteries of male eNOS-KO mice.

Flow-induced dilation was examined in isolated coronary arteries of endothelial nitric oxide (NO) synthase knockout mice (eNOS-KO) and wild-type (WT) mice. The basal tone of arteries (percentage of passive diameter) was significantly greater in eNOS-KO than in WT mice; their flow-induced dilations, however, were similar. Endothelial removal eliminated the dilations in vessels of both strains of mice. In arteries of WT mice, N(omega)-nitro-L-arginine methyl ester (L-NAME) (10(-4) M) or indomethacin (10(-5) M) alone, inhibited flow-induced dilation by approximately 50%, whereas their simultaneous administration abolished the responses. In arteries of eNOS-KO mice, flow-induced dilation was inhibited by approximately 40% with L-NAME. The residual portion (60%) of the response was eliminated by the additional administration of indomethacin. 7-Nitroindazole (10(-4) M) attenuated flow-induced dilation by approximately 40% in arteries of eNOS-KO mice, but did not affect responses in those of WT mice. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (3 x 10(-5) M) inhibited the L-NAME/7-nitroindazole-sensitive portion of the responses in arteries of eNOS-KO mice. Immunohistochemical evidence confirms the presence of neuronal NOS (nNOS) in the arterial endothelium of eNOS-KO mice. In conclusion, nNOS-derived NO, via activation of cGMP, together with prostaglandins, maintains flow-induced dilation in coronary arteries of male eNOS-KO mice.

Animals↗
PubMed2002

Different roles of PKC and MAP kinases in arteriolar constrictions to pressure and agonists.

Protein kinase C (PKC) and mitogen-activated protein (MAP) kinases have been implicated in the modulation of agonist-induced contractions of large vessels. However, their role in pressure- and agonist-induced constrictions of skeletal muscle arterioles, which have a major role in regulating peripheral resistance, is not clearly elucidated. Thus constrictions of isolated rat gracilis muscle arterioles (approximately 80 microm in diameter) to increases in intraluminal pressure and to norepinephrine (NE) or angiotensin II (ANG II) were assessed in the absence or presence of chelerythrine, PD-98058, and SB-203580 (inhibitors of PKC, p42/44 and p38 MAP kinase pathways, respectively). Arteriolar constriction to NE and ANG II were significantly reduced by chelerythrine (by approximately 90%) and unaffected by SB-203580, whereas PD-98058 decreased only ANG II-induced constrictions (by approximately 60%). Pressure-induced increases in wall tension (from 0.1 to 0.7 N/m) resulted in significant arteriolar constrictions (50% maximum) that were abolished by chelerythrine without altering smooth muscle intracellular Ca(2+) concentration ([Ca(2+)](i)) (fura 2 microfluorimetry). PD-98058 and SB-203580 significantly decreased the magnitude of myogenic tone (by 20% and 60%, respectively) and reduced the sensitivity of the myogenic mechanism to wall tension, causing a significant rightward shift in the wall tension-myogenic tone relationship without affecting smooth muscle [Ca(2+)i]. MAP kinases were demonstrated with Western blotting. Thus in skeletal muscle arterioles 1) PKC is involved in both myogenic and agonist-induced constrictions, 2) PD-98058-sensitive p42/44 MAP kinases modulate both wall tension-dependent and ANG II-induced constrictions, whereas 3) a SB-203580-sensitive p38 MAP kinase pathway seems to be specifically involved in the mechanotransduction of wall tension.

Angiotensin II↗
PubMedDate not supplied

Gender-specific regulation of cardiovascular function: estrogen as key player.

This review provides an overview of gender-specific differences in the incidence and development of cardiovascular diseases, including hypertension, atherosclerosis, heart failure and the corresponding myocardial remodeling. The review discusses the possible mechanisms by which estrogen affords a beneficial effect on cardiovascular function via genomic vs non genomic regulation; estrogen receptor-dependent vs estrogen receptor-independent pathways, specific signal transduction cascades, especially those involving protein kinase B (Akt) and mitogen activated protein kinase (MAPK), as well as their downstream targets, such as nitric oxide synthase, cyclooxygenase, cytochrome P450 (CYP), NADPH oxidase and superoxide dismutase. Having considered the essential role of the microcirculation in the control of vascular resistance in vivo, estrogen-related regulation of microvascular function and blood pressure is highlighted. Attention is focused on the effects of estrogen on pressure (myogenic)-dependent and flow/shear stress-dependent mechanisms of arterioles, which contribute significantly to the control of local blood flow and peripheral resistance via alterations in the release of endothelial mediators, such as nitric oxide, prostaglandins and endothelium-derived hyperpolarizing factor.

Animals↗