Cromakalim and pinacidil dilate small mesenteric arteries but not small cerebral arteries

1991 ◽  
Vol 261 (2) ◽  
pp. H287-H291 ◽  
Author(s):  
J. G. McCarron ◽  
J. M. Quayle ◽  
W. Halpern ◽  
M. T. Nelson

Small elevations in external K+ hyperpolarize and dilate small cerebral arteries. The hyperpolarization and dilation to K+ are blocked by barium (less than 0.1 mM). Since membrane hyperpolarization appears to be an important mechanism for dilation of these small cerebral arteries, we investigated the effects of the hyperpolarizing vasodilators, cromakalim and pinacidil, on isolated pressurized rat cerebral arteries (diameter of 158 +/- 5 microns at 50% of the systolic blood pressure). Cromakalim and pinacidil, which are potent relaxants of a variety of muscle types, were without effect on posterior cerebral arteries at concentrations that completely dilate similarly sized rat mesenteric arteries (diameter 134 +/- 6 microns at 50% of the systolic blood pressure). The mesenteric artery dilation to cromakalim and pinacidil was reversed by glibenclamide. However, unlike the cerebral arteries, mesenteric arteries did not exhibit a barium-sensitive dilation to external K+. Thus it appears that there may be differences in the types of K+ channels that are activated by dilating mechanisms in small cerebral and mesenteric arteries.

2013 ◽  
Vol 304 (11) ◽  
pp. H1446-H1454 ◽  
Author(s):  
Olan Jackson-Weaver ◽  
Jessica M. Osmond ◽  
Melissa A. Riddle ◽  
Jay S. Naik ◽  
Laura V. Gonzalez Bosc ◽  
...  

We have previously shown that hydrogen sulfide (H2S) reduces myogenic tone and causes relaxation of phenylephrine (PE)-constricted mesenteric arteries. This effect of H2S to cause vasodilation and vascular smooth muscle cell (VSMC) hyperpolarization was mediated by large-conductance Ca2+-activated potassium channels (BKCa). Ca2+ sparks are ryanodine receptor (RyR)-mediated Ca2+-release events that activate BKCa channels in VSMCs to cause membrane hyperpolarization and vasodilation. We hypothesized that H2S activates Ca2+ sparks in small mesenteric arteries. Ca2+ sparks were measured using confocal microscopy in rat mesenteric arteries loaded with the Ca2+ indicator fluo-4. VSMC membrane potential ( Em) was measured in isolated arteries using sharp microelectrodes. In PE-constricted arteries, the H2S donor NaHS caused vasodilation that was inhibited by ryanodine (RyR blocker), abluminal or luminal iberiotoxin (IbTx, BKCa blocker), endothelial cell (EC) disruption, and sulfaphenazole [cytochrome P-450 2C (Cyp2C) inhibitor]. The H2S donor NaHS (10 μmol/l) increased Ca2+ sparks but only in the presence of intact EC and this was blocked by sulfaphenazole or luminal IbTx. Inhibiting cystathionine γ-lyase (CSE)-derived H2S with β-cyano-l-alanine (BCA) also reduced VSMC Ca2+ spark frequency in mesenteric arteries, as did EC disruption. However, excess CSE substrate homocysteine did not affect spark activity. NaHS hyperpolarized VSMC Em in PE-depolarized mesenteric arteries with intact EC and also hyperpolarized EC E m in arteries cut open to expose the lumen. This hyperpolarization was prevented by ryanodine, sulfaphenazole, and abluminal or luminal IbTx. BCA reduced IbTx-sensitive K+ currents in freshly dispersed mesenteric ECs. These results suggest that H2S increases Ca2+ spark activity in mesenteric artery VSMC through activation of endothelial BKCa channels and Cyp2C, a novel vasodilatory pathway for this emerging signaling molecule.


1991 ◽  
Vol 11 (3) ◽  
pp. 371-379 ◽  
Author(s):  
Chiharu Tanoi ◽  
Yoshio Suzuki ◽  
Masato Shibuya ◽  
Kenichiro Sugita ◽  
Kaoru Masuzawa ◽  
...  

Vasoconstrictor effects of endothelin-1 (ET) were investigated in endothelium-denuded strips of cerebral (basilar and posterior cerebral) and mesenteric arteries of the dog. ET produced a concentration-dependent contraction in these arteries. Contractile responses to lower concentrations (below 3 × 10−10 M) of ET were significantly greater in the cerebral arteries than in the mesenteric artery. Inhibition by nifedipine of the contractile responses to ET was greater in the basilar artery than in the mesenteric artery. After the inhibition by 10−7 M nifedipine, the remaining responses to ET were similar in the two arteries. Cerebral arteries, but not the mesenteric artery, relaxed significantly from the resting level when placed in a Ca2+ -free solution containing 0.1 m M EGTA (0-Ca solution). Readdition of Ca2+ to the cerebral arteries placed in the 0-Ca solution caused a biphasic contraction that was sensitive to nifedipine. When 10−9 M ET was introduced before the Ca2+-induced contraction, this peptide produced only a very small contraction, but enhanced the Ca2+-induced contraction. The extent of the enhancement induced by ET was much greater in the cerebral arteries than in the mesenteric artery. These results indicate that the enhanced responses to ET in the cerebral arteries were dependent to a large extent on Ca2+ influx through voltage-dependent Ca2+ channels (VDCs). It is likely that the VDCs in these arteries are more activated in the resting state than those in the mesenteric artery.


2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Shan Shan Li ◽  
Fan Xing Zeng ◽  
Li Jun Shi

Objective To investigate the effect of exercise during pregnancy on L-type Ca2+ (CaV1.2) channel in mesenteric artery from spontaneously hypertensive rats (SHR) offspring. Methods Female (11 weeks old) and male (12 weeks old) SHR, female (11 weeks old) and male (12 weeks old) WKY rats were selected to use for breeding. The day when the vaginal bolt was found was considered day 1 of gestation. The pregnant rats were randomly divided into four groups: WKY sedentary group (WKY-SED), WKY exercise group (WKY-EX), SHR sedentary group (SHR-SED) and SHR exercise group (SHR-EX). The exercise groups were subjected to swimming at the first day of pregnancy, 1h/d,6 days/week for 3 weeks. The 6-month-old male offspring were operated with femoral arterial and venous cannulation, and the blood pressure after intravenous (i.v.) injection of CaV1.2 channel opener BayK8644 and blocker nifedipine were monitored in vivo. In vitro study, the mesenteric arteries were removed and used for isometric contraction studies. The non-selective NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 100 μM) was added after 60mM KCl measurement. To investigate the contribution of CaV1.2 channels in vascular tone regulation, the vascular responses to nifedipine (10−9–10−5M) were examined. Western blot was applied to examine the protein expression levels of CaV1.2 channel. Results (1) The mean arterial pressure(MAP) were higher in the 6M offspring of SHR-SED group than that of WKY-SED group (P<0.01), but there was no significant difference between the 6M offspring of SED and Ex groups. (2) The pressor responses induced by i.v. injection of BayK8644(0.1mg/Kg)were increased in the 6M offspring of SHR-SED group (P<0.05) compared with the WKY-SED group. Exercise during pregnancy markedly decreased the pressor responses in 6M offspring of SHR-EX group (P<0.05). (3) Compared with the 6M offspring of WKY-SED group, the depressor responses induced by i.v. injection of nifedipine(1mg/Kg)were increased in the 6M offspring of SHR-SED group (P<0.01). Exercise during pregnancy markedly attenuated the depressor responses in 6M offspring of SHR-EX group (P<0.05). (4) The isometric contraction study revealed that nifedipine induced concentration-dependent vasorelaxation in mesenteric artery precontracted with noradrenaline. The sensitivity of tissues to nifedipine in 6M offspring of SHR-SED group was significantly higher than that of WKY-SED group (P<0.01). Exercise during pregnancy normalized the increased sensitivity of tissues to nifedipine in 6M offspring of SHR (P<0.05). (5) Compared with the 6M offspring of WKY-SED group, the protein expression of CaV1.2α1C was significantly increased in SHR-SED group(P<0.01). Exercise during pregnancy markedly inhibited the expression of CaV1.2α1C in 6M offspring of SHR-EX group (P<0.05). Conclusions Pregnancy exercise has no significant effect on basic blood pressure in 6M offspring of SHR; but the increased function and protein expression of CaV1.2 channel in 6M offspring of SHR may be normalized by exercise during pregnancy.


2010 ◽  
Vol 299 (3) ◽  
pp. H624-H633 ◽  
Author(s):  
Alessandra Zulian ◽  
Sergey G. Baryshnikov ◽  
Cristina I. Linde ◽  
John M. Hamlyn ◽  
Patrizia Ferrari ◽  
...  

The Milan hypertensive strain (MHS) of rats is a model for hypertension in humans. Inherited defects in renal function have been well studied in MHS rats, but the mechanisms that underlie the elevated vascular resistance are unclear. Altered Ca2+ signaling plays a key role in the vascular dysfunction associated with arterial hypertension. Here we compared Ca2+ signaling in mesenteric artery smooth muscle cells from MHS rats and its normotensive counterpart (MNS). Systolic blood pressure was higher in MHS than in MNS rats (144 ± 2 vs. 113 ± 1 mmHg, P < 0.05). Resting cytosolic free Ca2+ concentration (measured with fura-2) and ATP-induced Ca2+ transients were augmented in freshly dissociated arterial myocytes from MHS rats. Ba2+ entry activated by the diacylglycerol analog 1-oleoyl-2-acetyl- sn-glycerol (a measure of receptor-operated channel activity) was much greater in MHS than MNS arterial myocytes. This correlated with a threefold upregulation of transient receptor potential canonical 6 (TRPC6) protein. TRPC3, the other component of receptor-operated channels, was marginally, but not significantly, upregulated. The expression of TRPC1/5, components of store-operated channels, was not altered in MHS mesenteric artery smooth muscle. Immunoblots also revealed that the Na+/Ca2+ exchanger-1 (NCX1) was greatly upregulated in MHS mesenteric artery (by ∼13-fold), whereas the expression of plasma membrane Ca2+-ATPase was not altered. Ca2+ entry via the reverse mode of NCX1 evoked by the removal of extracellular Na+ induced a rapid increase in cytosolic free Ca2+ concentration that was significantly larger in MHS arterial myocytes. The expression of α1/α2 Na+ pumps in MHS mesenteric arteries was not changed. Immunocytochemical observations showed that NCX1 and TRPC6 are clustered in plasma membrane microdomains adjacent to the underlying sarcoplasmic reticulum. In summary, MHS arteries exhibit upregulated TRPC6 and NCX1 and augmented Ca2+ signaling. We suggest that the increased Ca2+ signaling contributes to the enhanced vasoconstriction and elevated blood pressure in MHS rats.


2018 ◽  
Vol 132 (4) ◽  
pp. 461-474 ◽  
Author(s):  
Anna K.J. Gradel ◽  
Max Salomonsson ◽  
Charlotte M. Sørensen ◽  
Niels-Henrik Holstein-Rathlou ◽  
Lars Jørn Jensen

Abdominal obesity and/or a high intake of fructose may cause hypertension. K+ channels, Na/K-ATPase, and voltage-gated Ca2+ channels are crucial determinants of resistance artery tone and thus the control of blood pressure. Limited information is available on the role of K+ transporters in long-term diet-induced hypertension in rats. We hypothesized that a 28-week diet rich in fat, fructose, or both, will lead to changes in K+ transporter expression and function, which is associated with increased blood pressure and decreased arterial function. Male Sprague–Dawley (SD) rats received a diet containing normal chow (Control), high-fat chow (High Fat), high-fructose in drinking water (High Fructose), or a combination of high-fat and high-fructose diet (High Fat/Fruc) for 28 weeks from the age of 4 weeks. Measurements included body weight (BW), systolic blood pressure (SBP), mRNA expression of vascular K+ transporters, and vessel myography in small mesenteric arteries (SMAs). BW was increased in the High Fat and High Fat/Fruc groups, and SBP was increased in the High Fat/Fruc group. mRNA expression of small conductance calcium-activated K+ channel (SKCa), intermediate conductance calcium-activated K+ (IKCa), and Kir2.1 inward rectifier K+ channels were reduced in the High Fat/Fruc group. Reduced endothelium-derived hyperpolarization (EDH)-type relaxation to acetylcholine (ACh) was seen in the High Fat and High Fat/Fruc groups. Ba2+-sensitive dilatation to extracellular K+ was impaired in all the experimental diet groups. In conclusion, reduced expression and function of SKCa, IKCa, and Kir2.1 channels are associated with elevated blood pressure in rats fed a long-term High Fat/Fruc. Rats fed a 28-week High Fat/Fruc provide a relevant model of diet-induced hypertension.


1998 ◽  
Vol 37 (08) ◽  
pp. 268-271
Author(s):  
B. Caner ◽  
E. Atalar ◽  
A. Karanfil ◽  
L. Tokgözoğlu ◽  
E. L. Ergün

Summary Aim: Dobutamine as a predominant beta-1 agonist increases heart rate and myocardial contractility and at sufficient high doses, it also increases systolic blood pressure. This study was undertaken to describe instances of paradoxical hypotension during dobutamine infusion for TI-201 myocardial perfusion SPECT study and the relationship between scintigraphic findings and hypotension occurred during dobutamine infusion. Methods: In 201 consecutive patients unable to perform adequate exercise, dobutamine TI-201 myocardial SPECT was performed. Dobutamine was infused starting from 10 μg/kg/min increasing to 40 μg/kg/min. Paradoxical hypotension was defined as a decrease in systolic blood pressure ≥ 20 mmHg compared with baseline study. Results: Paradoxical hypotension was observed in 40 patients (Group A) out of 201 (19.9%) while no significant change in systolic blood pressure was detected in the remaining 161 patients (Group B). Mean maximum fall in systolic blood pressure was 39 ± 18 mmHg (range: 20-90). In 33 of 40 patients (83%) with paradoxical hypotension, scintigraphy was normal compared to 131 (81%) of the remaining 161 patients. In patients of Group A, angiography, echocardiography and tilt table tests were performed in 13, 11 and 6 patients respectively. Nine of 13 angiographic evaluations (69%), 10 of 11 echocardiographic evaluations (91%), all of the tilt table tests were normal. Additionally, all of the patients of Group A were clinically followed up at least 6 months after the myocardial perfusion scintigraphy. None of the patients had a cardiac event except one patient during the follow-up period. Conclusion: Paradoxical hypotension during dobutamine infusion for myocardial scintigraphy is not an uncommon finding and up to 19.9% patients may develop such hypotension. To maximize test safety, precautions should be taken during dobutamine myocardial stress test, since remarkable decrease in systolic blood pressure may occur. Unlike hypotension occurring with exercise test, hypotension response to dobutamine is not always a marker for coronary artery disease.


Author(s):  
Somesh Raju ◽  
Rina Kumari ◽  
Sunita Tiwari ◽  
NS Verma

Background: Interarm systolic blood pressure difference more than 10 mm of Hg is predictor of cardiovascular and metabolic risk. Despite of sufficient physical activity there is high prevalence of obesity in police personal because of stressful working environment. No studies have addressed the significance of interarm pressure difference among them. Therefore, the present study conducted to access the relation of interarm blood pressure difference with obesity in police personnel. Aims and Objective: To estimate the interarm pressure difference in police personal to see its association with their obesity. Material and Method: This cross-sectional observational study done on 245 police workers in PAC, Sitapur, India. Subjects having more than ten years of working experience were included in study. Anthropometric measurements of subject recorded by following standard protocol. Measurement of systolic pressure in both arm recorded simultaneously by mercury sphygmomanometer. Available data analyze and expressed in percentage, mean with SD and chi square test to see the significance of association. Results: According to anthropometric results of subjects 77.14 prcent subjects were having generalised obesity and 82.04 percent of subjects having abdominal obesity. 34.29 percent of subjects showed abnormally high (?10 mmHg) inter-arm systolic blood pressure difference. Both type of obesity showed positive association with blood sugar level but no association with interarm pressure difference. Conclusion: Interarm blood pressure difference is greater in individual having obesity or prolong duration of service. Such subjects are more susceptible to develop coronary artery disease or peripheral arterial disease in future. Early screening can help to detect the vascular events likely to occur in the future Keywords: Body mass index, Waist circumference, Interarm pressure difference, Random blood sugar


2019 ◽  
Vol 10 (01) ◽  
pp. 33-44
Author(s):  
N.L.G. Sudaryati ◽  
I P. Sudiartawan ◽  
Dwi Mertha Adnyana

The aim of the study was to determine the effectiveness of giving hydrotherapi foot soak in hypertensive patients. The study was conducted with one group pretestposttest design without a control group by measuring blood pressure (pretest) before being given an intervention in the form of foot soak hydrotherm against 15 people with hypertension in Banjar Sri Mandala, Dauhwaru Village, Jembrana Subregency. Then do the blood pressure measurement again (posttest) after finishing the intervention. After the study was completed, the results showed that before the hydrotherapi foot bath intervention, there were 0% of patients classified as normal, 13.32% in prehypertension category, 60.08% in hypertension category I and 26.60% in hypertension category II. After the intervention was given, there were 13.32% of the patients classified as normal, 66.68% in the prehypertension category, 20.00% in the first category of hypertension and no patients belonging to the second grade hypertension category. There is a decrease of 20-30 mmHg for systolic blood pressure and 0-10 mmHg for diastolic blood pressure after intervention. Based on the results of the study it can be concluded that the hydrotherapi foot bath is effectively used to reduce blood pressure in hypertensive patients in the Banjar Sri Mandala, Dauhwaru Village, Jembrana District.


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