Angiotensin II effect on 22Na+ transport in vascular smooth muscle cells

It is well established that angiotensin II (AII) rapidly increases free cytosolic Ca2+ in vascular smooth muscle cells (VSMCs). Several studies have indicated that the hormone also plays a role in Na+-K+ regulation of these cells. In this study, we explored the mechanism of AII effect on 22Na+ transport in cultured rat VSMCs. The 22Na+ washout from these cells was described by three exponents with exponential factors k1 greater than k2 greater than k3. In 1.8 mM Ca2+ medium, AII (10(-9)-10(-6) M) increased (in a dose response manner) the k1 value, and consequently the initial washout rate constant (kei) for the isotope. AII had no effect on kei in Ca2+-deficient medium or in the presence of ouabain. Amiloride (10(-3) M) and verapamil (10(-5) M) abolished the AII induced increase in kei. These findings are consistent with angiotensin II stimulation of an amiloride-sensitive Na+ transport, which is likely to represent the Na+/H+ antiport. In cultured VSMCs, the sustained stimulation by AII of this transport system requires the presence of extracellular Ca2+ and its influx into these cells.     

Stimulatory effect of serum on 86Rb washout from vascular smooth muscle cells in culture

In order to elucidate the effect of serum on passive K permeability of vascular smooth muscle cells (VSMC) membrane, outward passive K permeability yielded as washout rate constant (Kc) of 86Rb washout, was measured in the presence and in the absence of cation transport modulators using VSMC in culture. The overall Kc of 86Rb washout subjected to 1% serum was significantly larger than that in controls. This stimulated Kc was substantially blunted in the presence of 10(-4) M amiloride and was partially inhibited with 5 x 10(-4) M bumetanide. Angiotensin II of 10(-5) M exerted to a lesser extent, a similar significant stimulatory effect on Kc of 86Rb washout, which effect was inhibited with application of amiloride. Additionally, Ca-antagonist, 10(-5) M nifedipine reduced serum-stimulated Kc to the basal level. It is concluded that both serum and angiotensin II increase K permeability in cultured VSMC. A part of this effect of serum may be attributable to angiotensin II in the serum. Furthermore, it is suggested that the stimulatory effect of serum on membrane permeability may be exerted, at least in part, via activation of both Na-H antiport and Na-K co-transport, possibly through mechanisms in conjunction with intracellular Ca.     

Blockade of Na+/H+ exchanger contracts the portal vein of spontaneously hypertensive and Wistar Kyoto rats

It has been claimed that the activity of Na+/H+ exchanger (NHE) is altered in spontaneously hypertensive rats (SHR) suggesting a possible role for it in the pathophysiology of hypertension. The purpose of this study has been to investigate the effect of blockade of NHE on the noradrenaline (NA) and 26K+ induced tone and on the recovery of tone from acid induced contractions in the portan vein of spontaneously hypertensive rats (SHR) as compared to their controls of Wistar Kyoto rats (WKY). Blockade of NHE by 10(-4) dimethylamiloride (DMA) raised the tone of NA and 26K+ activated preparation of both strains, the contractions being higher with NA activation. Total blockade of NHE by replacement of Na in solution with N-methy-D-Glucamine (NMDG) raised the tone of the NA activated preparations by 45+/-10%, n=8, P<0.01 and 33+/-4%, n=12, P < 0.01 in SHR and WKY respectively. The time for 50% relaxation from NH4Cl washout contraction was significantly prolonged by 10(-5) and 10(-4) M DMA in both strains under NA or 26K+ activation. DMA effect was greater on NA than on 26K+ activated preparations, and was not significantly different when comparing SHR to WKY results. In conclusion the results reported in this study indicate that NHE has similar activity in WKY and SHR portal veins and that its blockade contracts both preparations. Therefore, it is unlikely that increased NHE activity, acting directly on vascular smooth muscle tone, could be a primary cause for hypertension.     

Individualities in post-serotonin attenuation and Na+/K+ pump activity in vascular smooth muscle

Prior treatment with serotonin (10(-8)-10(-7) M for 6 min) attenuated responses of rabbit mesenteric arteries to norepinephrine (NE) by 18-62%, but was without effect on the responses of the rabbit aorta. K+ relaxation responses in the mesenteric arteries were enhanced by serotonin, but in the aortic strips K+ relaxation occurred either before or after treatment with serotonin. Maximum relaxation to monensin was similar in the two tissues. Post-serotonin attenuation and K+ and monensin relaxation were blocked by ouabain, indicating that they depended on Na+/K+ pump stimulation. Intracellular Na+ contents (Nai) were determined in the vessels by the Li substitution method. Nai was greater, and was increased to a greater extent by serotonin and K(+)-free physiological salt solution in the mesenteric artery compared to the aorta, suggesting that the cell membrane of the mesenteric artery is leakier to Na+ than is that of the aorta. We conclude that the absence of post-serotonin attenuation in the aorta results from the failure of serotonin to increase Nai and thereby to stimulate the Na+/K+ pump in this tissue. This study demonstrates that important individualities in vascular smooth muscle reactivity even in the same animal may result from differences in membrane permeability to sodium.     

Proliferation of aortic smooth muscle cells and renin-angiotensin system in SHR rats

目的：探讨ＳＨＲ大鼠主动脉平滑肌细胞（ＡＳＭＣ）异常增殖和肾素血管紧张素系统（ＲＡＳ）的关系．方法：测定血管紧张素Ｉ（Ａｎｇ）、卡托普利（Ｃａｐ）、沙拉新（Ｓａｒ）对培养的ＳＨＲ、ＷＫＹＡＳＭＣ增殖和Ａｎｇ、血管紧张素转化酶（ＡＣＥ）的影响．结果：Ａｎｇ在２％血清培养基中可刺激ＳＨＲＡＳＭＣ增生．ＳＨＲＡＳＭＣ分裂增殖能力比ＷＫＹ强，ＳＨＲＡＳＭＣＲＡＳ处于高功能状态．Ｃａｐ长期（４周）干预显著抑制ＳＨＲＡＳＭＣ异常增殖和Ａｎｇ、ＡＣＥ活性，Ｓａｒ长期干预同样抑制ＳＨＲＡＳＭＣ的增殖和ＡＣＥ活性，但Ａｎｇ水平反而升高．Ｃａｐ短期（２４小时）干预不影响两种大鼠ＡＳＭＣＲＡＳ．结论：Ｃａｐ和Ｓａｒ长期干预通过减少ＳＨＲＡＳＭＣＡｎｇ生成或阻断Ａｎｇ和特异受体结合，抑制其异常增殖．     

Endothelial-dependent sexual dimorphism in vascular smooth muscle: role of Mg2+ and Na+.

1. In isolated aortae of the male rat [Mg2+]o withdrawal and concomitant reduction in [Na+]o (to 84 mM) induced significant increases of basal tone, but, surprisingly, this did not occur in intact aortae removed from female rats. Such tension development, however, was observed in endothelium-denuded aortic preparations from both sexes. These observed gender-related differences were not dependent on animal strain or types of tissue preparations. 2. No tension development was observed in aortae obtained from castrated males treated with oestradiol. Aortic tissues of sexually-immature male and female rats exhibited marked tension development when exposed to 0 mM [Mg2+]o and low [Na+]o. 3. Tension development in Mg(2+)-free, low-Na+ media was not tachyphylactic and completely dependent on extracellular Ca2+; addition of 1.2 mM Mg2+ to the Mg2+ and Na(+)-deficient incubation media relaxed the increase in tension to a normal basal level. 4. Two known endothelial-derived relaxant factor (EDRF) inhibitors, methylene blue and haemoglobin, induced tension development in female aortae with intact endothelium exposed to Mg(2+)-Na+ deficient media, while use of a specific inhibitor of EDRF-derived nitric oxide, viz., NG-monomethyl-L-arginine (L-NMMA), resulted in potentiation of tension development in male, but not in female, aortae. This effect of L-NMMA was antagonized by L-arginine. 5. The Ca ionophore, A23187, partially relaxed contractile responses in male aortae (with intact endothelium) which were followed by potentiated contractions. Endothelium-dependent vasodilator responses to A23187 (10(-10)-10(-6) M) of aortic rings from male or female rats in normal Krebs-Ringer bicarbonate solution were not different.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of the K+ channel blocker tedisamil on 86Rb efflux induced by cromakalim,high potassium and noradrenaline,and on mechanical tension in rabbit isolated vascular smooth muscle

Summary Tedisamil, a new bradycardic agent with an inhibitory action on K⁺ channels in cardiac muscle, was found to inhibit in a non-competitive manner the relaxation induced by the K⁺ channel opener cromakalim in noradrenaline-stimulated helical strips from rabbit aortae. Tedisamil tended to be more potent in this respect than glibenclamide; the latter however competitively antagonized the cromakalim-induced relaxation. In rabbit aorta preloaded with ⁸⁶Rb as a marker of K⁺, 10 mol/l tedisamil inhibited the ⁸⁶Rb efflux induced by 10 mol/l cromakalim. — While the ⁸⁶Rb efflux evoked by depolarization with 100 mmol/l K⁺ aspartate was inhibited by tedisamil, too, the rise of ⁸⁶Rb efflux induced by noradrenaline was unaffected by the drug.In non-stimulated rabbit aorta, tedisamil increased mechanical tension in a concentration-dependent manner (EC₅₀ for peak contractions: 32 mol/l; for maintained tension: 24 mol/l), and enhanced ⁸⁶Rb efflux. Both stimulant actions were antagonized by the calcium antagonist diltiazem.In conclusion, tedisamil affects different K⁺ channels in vascular smooth muscle. Its stimulant effects are assumed to be secondary to membrane depolarization and subsequent activation of voltage-dependent Ca²⁺ channels.Supported by the Deutsche Forschungsgemeinschaft Send offprint requests to V. A. W. Kreye at the above address     

Methylphenidate reduces impulsive behaviour in juvenile Wistar rats, but not in adult Wistar, SHR and WKY rats

Rationale Impulsivity is a core symptom of attention deficit/hyperactivity disorder (ADHD). The spontaneously hypertensive rats (SHR) is a strain commonly used as an animal model of ADHD. However, there is no clear evidence that psychostimulants, which are used for treatment of ADHD, reduce impulsivity in SHR. Because ADHD mainly affects children, it may be relevant to study psychostimulants on juvenile animals. Objectives Using tolerance to delay of reward as index of impulsivity, the effects of methylphenidate were assessed in adult SHR, Wistar Kyoto (WKY) and Wistar rats and in juvenile Wistar rats. Materials and methods Animals were trained in a T-maze to choose between a small-but-immediate and a large-but-delayed reward. Adult SHR, WKY and Wistar rats were compared for their ability to tolerate a 15-s delay. The effect of methylphenidate on the tolerance to a 30-s delay was studied in adult rats of the three strains and in juvenile (4.5 to 6.5-week-old) Wistar rats. Results In adult rats, the waiting ability was lower in SHR than in control strains. Waiting ability was improved by methylphenidate (3 and 5 mg/kg) in juveniles, but not by methylphenidate (3 mg/kg) in adults. Conclusions These data support the idea that SHR are more impulsive than control strains. However, at the dose studied, methylphenidate fails to improve tolerance to delay in adult rats whatever the strain used. The reduction of impulsivity induced by methylphenidate in juvenile Wistar rats indicates that juvenile animals may be suitable for testing the therapeutic potential of drugs intended to the treatment of ADHD in children.     

Dissociation between vascular oxidative stress and cardiovascular function in Wistar Kyoto and spontaneously hypertensive rats

It has not been completely demonstrated if hypertension may, in part, develop as a result of increased oxidative stress (OS), inflammation and little is known about the short-term effects of antioxidant therapy. This study was designed to appreciate the effect of 7 days vitamin C-enriched diet (5 g/kg/day) on hemodynamic function and vascular OS in normotensive Wistar Kyoto rats and hypertensive rats (SHR). Aorta NAD(P)H oxidase activity was determinate and free radicals evaluated by electron spin resonance with a spin probe CP-H. Matrix metalloproteinase-1 (MMP-1) and monocyte chemoattractant protein-1 (MCP-1) expression were measured. The treatment with vitamin C did not change arterial pressure in SHR but prevented the increase in OS levels in SHR aortas. MMP-1 and MCP-1 expressions were more intense in the media of SHR aortas than in those of WKY rats but these expressions were not modified by vitamin C-pretreatment. Vitamin C-pretreatment was not able to protect heart against in vitro ischemia-reperfusion dysfunctions. These data may suggest that treatment with high doses of vitamin C in SHR can limit over-production of reactive oxygen species; however this effect was not accompanied with changes in arterial pressure and protection against I-R dysfunctions. Dissociation between vascular oxidative stress and cardiovascular function may be evoked.     

自发性高血压大鼠主动脉平滑肌细胞异常增殖和局部肾素—血管？…

目的：探讨ＳＨＲ大鼠主动脉平滑肌细胞（ＡＳＭＣ）异常增殖和肾素－血管紧张素系统９ＲＡＳ）的关系。方法：测定血管紧张素Ⅱ（Ａｎｇ）、卡托普利（Ｃａｐ）、沙拉新（Ｓａｒ）对培养的ＳＨＲ、ＷＫＹ ＡＳＭＣ增殖的Ａｎｇ、血管紧张素转化酶（ＡＣＥ）的影响，结果：Ａｎｇ在２％血清培养基中可刺激ＳＨＲ ＡＳＭＣ增生，ＳＨＲ ＡＳＭＣ分裂增殖能力比ＷＫＹ强，ＳＨＲ ＡＳＭＣ ＲＡＳ处于高功能状态。Ｃａｐ长期（４周     

Anticardiolipin antibodies in spontaneously hypertensive rats (SHR), stroke-prone SHR and normal Wistar rats

1. Anticardiolipin antibodies (ACA) can be detected in the serum of patients with autoimmune disturbances, ischaemic heart disease, myocardial infarction, neurological disorders and other medical conditions. Elevated values of these autoantibodies can be associated with recurrent fetal loss, arterial and venous thrombosis and thrombocytopenia. 2. In the present study, we investigated the presence of ACA in three rat strains, namely normal Wistar rats (WR), spontaneously hypertensive rats Okamoto-Aoki (SHR) and stroke-prone SHR (SHRSP). All animals were examined at four ages: 1, 4, 10 and 12 months of age. Anticardiolipin antibodies were determined by ELISA. 3. Anticardiolipin antibody levels in normal WR, which were used as controls, were lowest at 1 month and increased significantly from the 4th month on. At the prehypertensive age (1 month), ACA levels in SHR and SHRSP were significantly higher compared with control WR, decreased with age and were significantly lower at 4, 10 and 12 months compared with age-matched WR. 4. These differences may be a result of immunological disorders in SHR.     

The dualistic mode of action of the vasodilator drug,nicorandil, differentiated by glibenclamide in 86Rb flux studies in rabbit isolated vascular smooth muscle

Summary (1) In rabbit isolated aorta, the effects of the antianginal drug, nicorandil, of the K⁺ channel opener, cromakalim, and of the nitrovasodilator, sodium nitroprusside, on ⁸⁶Rb efflux and on contractile force were compared. (2) In ion flux studies using ⁸⁶Rb as a marker of K⁺ ions, both nicorandil and cromakalim, but not sodium nitroprusside, increased the efflux of ⁸⁶Rb in non-stimulated preparations. The increase of membrane K⁺ conductance induced by nicorandil and cromakalim was totally suppressed by 10^–5 mol/l of the sulfonylurea derivative, glibenclamide. (3) The vasoconstrictor drug, noradrenaline (3 × 10^–7 mol/l), effectively increased the rate of ⁸⁶Rb efflux. This stimulatory response was unaffected by glibenclamide, but was totally inhibited by Ca²⁺ depletion suggesting that the activation of Ca²⁺-sensitive K⁺ channels was responsible for this action of noradrenaline. (4) Sodium nitroprusside and nicorandil, the latter in the presence of glibenclamide to suppress the glibenclamide-sensitive stimulatory component on ⁸⁶Rb efflux, antagonized the noradrenaline-induced increase in ⁸⁶Rb efflux, while cromakalim in the presence of glibenclamide had no effect. (5) All of the vasodilators relaxed rabbit aortic strips contracted by 10^–7 mol/l noradrenaline in a concentration-dependent manner. (6) The vasodilatory response to cromakalim was antagonized by glibenclamide, whereas the relaxant action of nicorandil and of sodium nitroprusside remained unaffected. (7) These results demonstrate that under particular experimental circumstances, nicorandil can behave in vascular smooth muscle both as an opener of glibenclamide-sensitive K⁺ channels, and as a directly acting nitrovasodilator which acts via reduction of cellular calcium levels. Nevertheless, its vasorelaxant action seems to depend primarily on its nitrovasodilator-like properties. (8) ⁸⁶Rb efflux studies are a suitable technique to differentiate between the cellular actions of vasodilators involving a reduction of intracellular calcium such as the nitrovasodilators, or acting similarly as cromakalim, i. e. presumably via opening of K⁺ channels. Supported by The Deutsche Forschungsgemeinschaft Offprint requests to V. A. W. Kreye at the above address     

The diverse effects of cromakalim on tension and 86Rb efflux in canine arterial smooth muscle.

1. To characterize further the K+ channels opened by cromakalim in arterial smooth muscle, the effects of cromakalim on tension and 86Rb efflux were compared in endothelium-denuded strips of coronary, mesenteric and middle cerebral (MC) arteries of the dog. 2. Cromakalim relaxed strips precontracted with 20.9 mM K+. The maximum relaxation induced by cromakalim varied in the arteries used; 94% in the coronary artery, 60% in the mesenteric artery and only 38% in the MC artery. Cromakalim failed to relax arterial strips precontracted with 65.9 mM K+. 3. When the effects of cromakalim on 86Rb efflux were determined in 20.9 mM K(+)-contracted strips, cromakalim-induced relaxations were accompanied by a large increase in 86Rb efflux in the coronary artery, by a small increase in the mesenteric artery but by an apparent decrease in the MC artery. 4. When 10(-7) M nifedipine was added to 20.9 mM K(+)-contracted strips, to inactivate Ca2(+)-activated K+ (KCa) channels, cromakalim produced a greater increase (measured from the point at which cromakalim was administered) in 86Rb efflux than in the absence of nifedipine, suggesting that the effects of cromakalim on 86Rb efflux from the 20.9 mM K(+)-contracted strips may be the resultant of two opposing effects: an increased 86Rb efflux perhaps due to the opening of ATP-sensitive K+ (KATP) channels, and a decreased efflux due to the closing of KCa channels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes of vascular smooth muscle reactivity in hypertensive rats

Mechanical responses produced by high potassium solution (high-K), norepinephrine (noradrenaline; NA) and phenylephrine (Phe) were examined in the thoracic aorta isolated from control (WKY) and spontaneously hypertensive rats (SHR). In the SHRs the tissues showed increased sensitivity to high potassium compared with those from the control rats. Mechanical removal of endothelium in tissues from the controls did not change the response. The effects produced by NA and Phe were also increased in tissues from SHRs. The amplitudes of contractions were enhanced after removal of the endothelium in tissues from the controls. The relaxation in response to endothelium-dependent vasodilators (acetylcholine and histamine) was significantly depressed in aortic rings from SHRs. Experiments using modified sandwich preparations suggest that the defect in the relaxant ability of vascular smooth muscle is coupled to a reduced functionality of the endothelium.     

Ca2+ localization and sensitivity in vascular smooth muscle

An increase in cytosolic Ca2+ level ([Ca2+]i) is a prerequisite for smooth muscle contraction. Simultaneous measurements of [Ca2+]i and muscle tension give direct information on the Ca2+ regulation of smooth muscle. The photoprotein aequorin and the fluorescent Ca2+ indicator fura-2 are widely used for this purpose. Although there are some inconsistencies between the results obtained with these two indicators, comparison between [Ca2+]i and muscle tension in vascular smooth muscle indicates that stimulation of alpha-adrenoceptors increases, whereas stimulation of beta-adrenoceptors decreases, both the Ca2+ sensitivity of contractile elements and [Ca2+]i. Thus, as Hideaki Karaki explains, contractility of vascular smooth muscle may be regulated not only by [Ca2+]i but also by the Ca2+ sensitivity of the contractile elements.     

Evidence for furosemide-sensitive active chloride transport in vascular smooth muscle

An inhibitor of Cl^? transport, furosemide, interfered potently with the ³⁶Cl steady state exchange in rabbit aortic tissue. On long-term incubation with furosemide, [Cl^?]_i decreased and E_Cl increased, thereby approaching the resting membrane potential of vascular smooth muscle. Electrophysiological microelectrode studies on rabbit pulmonary arteries revealed a hyperpolarization of 5.5 mV in the presence of furosemide. These findings provide evidence for an inwardly directed chloride pump operating in vascular smooth muscle.     

Comparison of receptors and enzymes regulating cholesterol levels in liver between SHR/NDmcr-cp rats and normotensive Wistar Kyoto rats at ten weeks of age

The spontaneously hypertensive rat (SHR)/NDmcr-cp (SHR-cp), which is a metabolic syndrome model rat, was reported to show hypercholesteremia, as compared with lean littermates. The serum total cholesterol level in SHR-cp at 18 weeks of age is higher than that of normotensive Wistar Kyoto rat (WKY), but that in SHR-cp at 10 weeks of age is the same. The objective of this study is to clarify whether there are differences in the system regulating serum cholesterol levels between SHR-cp and WKY at 10 weeks of age. Total serum cholesterol levels, and cholesterol levels of high density lipoprotein (HDL), low density lipoprotein (LDL), and very low density lipoprotein (VLDL) were similar in the two strains. However, the cholesterol levels in the liver of SHR-cp were lower than those of WKY. Next, mRNA levels of receptors (scavenger receptor class B type 1 [SRB1], LDL receptor [LDLR]) involved in uptake from serum to liver or enzymes of cholesterol catabolism (CYP7A1 and CYP8B1) and biosynthesis (mevalonate pyrophosphate decarboxylases [MPD]) in liver were compared between SHR-cp and WKY. High levels of MPD and LDLR and low levels of SRB1 were shown in SHR-cp, as compared with WKY. CYP7A1 and CYP8B1 levels were similar between SHR-cp and WKY. These results suggest that the serum cholesterol level in SHR-cp by the balance or regulation between the rise in cholesterol uptake and reduction in cholesterol biosynthesis in the liver is the same as that in WKY.     

Regulation of 86Rb+ ion transport across polarized human colonocytes by bis-phenolic compounds

1. Phenolphthalein, a well-known laxative, stimulates the secretion of Na+ and Cl- ions and accompanying water into the intestinal tract. Measurement of 86Rb+ efflux from several, but not all, cell types indicates that phenolphthalein also results in release of cellular K+ ions. 2. In the present study, the transport of 86Rb+ across human colonocyte cells (T84) cultured on trans-well inserts was examined. The T84 cells were cultured until they developed tight junctions and a high trans-epithelial resistance. 3. Results show that phenolphthalein applied to the apical, but not the basolateral, surface of cells causes the release of 86Rb+ from the apical surface. Basolateral treatment of cells with phenolphthalein had no effect on the release of 86Rb+. 4. Simultaneously with the increased 86Rb+ efflux, indirect evidence of enhanced Na+/K+-ATPase activity was also observed. 5. Although ouabain inhibited the increased Na+ pump activity, it did not affect apical 86Rb+ release. 6. As evidenced by near steady state 86Rb+ uptake data, the increased Na+/K+-ATPase activity was insufficient to restore intracellular concentrations of K+ in the presence of phenolphthalein. 7. 4,4(9-Fluorenylidene)diphenol, a homologue of phenolphthalein, had a similar effect on 86Rb+ transport by T84 cells. 8. These results indicate a primary stimulation of 86Rb+ efflux from the apical surface of polarized T84 cells by apically applied bis-phenolic compounds. 9. A secondary stimulation of the basolateral Na+/K+-ATPase is thought to result from intracellular Na+ increase, as documented in several other cell types exposed to bis-phenolic compounds, although not directly measured in these experiments. 10. The results also indicate that bis-phenolic compounds interact specifically with some apical but not basolateral membrane structures in regulating 86Rb+ efflux from polarized T84 cells.     

Chronic nicotine treatment enhances vascular smooth muscle relaxation in rats

Aim:

To investigate the effect of chronic nicotine treatment on vascular function and to identify the underlying mechanisms.

Methods:

Adult rats were treated with nicotine (3 mg·kg⁻¹·d⁻¹, sc) for 6 weeks. After the rats were sacrificed, aortic rings were prepared for detecting vascular reactivity, and thoracic aorta and periaortic fat samples were collected for histological and molecular biology studies.

Results:

Chronic nicotine treatment significantly reduced periaortic fat, and specifically enhanced smooth muscle relaxation without altering the aortic adventitial fat and endothelium function. Pretreatment with the soluble guanylyl cyclase inhibitor ODQ (3 μmol/L) or PKG inhibitor Rp-8-Br-PET-cGMP (30 μmol/L) abolished the nicotine-induced enhancement of smooth muscle relaxation, whereas the cGMP analogue 8-Br-cGMP could mimic the nicotine-induced enhancement of smooth muscle relaxation. However, the chronic nicotine treatment did not alter PKG protein expression and activity in aortic media.

Conclusion:

Chronic nicotine treatment enhances vascular smooth muscle relaxation of rats via activation of PKG pathway.