Association of gene polymorphisms in microRNA with blood pressure responses to salt and potassium intake / 西安交通大学学报(医学版)

【Objective】 To investigate the relationship of miRNA gene polymorphisms with blood pressure (BP) responses to the sodium and potassium diet intervention. 【Methods】 In 2004, we recruited 514 participants from 124 families in seven villages of Baoji, Shaanxi Province, China. All subjects were given a three-day normal diet, followed by a seven-day low-salt diet, a seven-day high-salt diet, and finally a seven-day high-salt and potassium supplementation. A total of 19 miRNA single nucleotide polymorphisms (SNPs) were selected for analysis. 【Results】 Throughout the sodium-potassium dietary intervention, the BP of the subjects fluctuated across all phases, showing a decrease during the low-salt period and an increase during the high-salt period, followed by a reduction in BP subsequent to potassium supplementation during the high-salt diet. MiR-210-3p SNP rs12364149 was significantly associated with systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) responses to low-salt diet. MiR-4638-3p SNP rs6601178 was significantly associated with SBP while miR-26b-3p SNP rs115254818 was significantly associated with MAP responses to low-salt intervention. In addition, miR-26b-3p SNP rs115254818 was significantly correlated with SBP, DBP and MAP responses to high-salt intervention. MiR-1307-5p SNPs rs11191676 and rs2292807 were associated with SBP and MAP responses to high-salt diet. MiR-4638-3p SNP rs6601178, miR-210-3p SNP rs12364149, miR-382-5p SNP rs4906032 and rs4143957 were significantly associated with SBP response to high-salt diet. In addition, miR-26b-3p SNP rs115254818 was significantly associated with SBP, DBP and MAP responses to potassium supplementation. MiR-1307-5p SNPs rs11191676, rs2292807, and miR-19a-3p SNP rs4284505 were significantly associated with SBP responses to high-salt and potassium supplementation. 【Conclusion】 miRNA gene polymorphisms are associated with BP response to sodium and potassium, suggesting that miRNA genes may be involved in the pathophysiological process of salt sensitivity and potassium sensitivity.

Comparison of efficacy of Lignocaine 1.5 mg/kg & Dexmedetomidine 1 μg/kg in attenuating the hemodynamic pressure response to laryngoscopy & intubation

Background: Dexmedetomidine attenuates the hemodynamic stress response tolaryngoscopy and intubation more effectively compared with Lignocaine without any deleterious effects. To study the efficacy of Lignocaine 1.5 mg/kg & Dexmedetomidine 1 μg/kg in attenuating the hemodynamic pressure response to laryngoscopy & intubation. Material and Methods: A total of 100 American Society of Anesthesiologists (ASA) physical status I and II patients aged between 18 and 50 years undergoing elective surgery were enrolled in the study. Patients posted for elective surgery were randomly selected and divided into two groups. Group L = 50 Patients had given 1.5mg/kg Lignocaine; Group D = 50 Patients had given 1µg / kg Dexmedetomidin. Results: In Dexmedetomidine group, HR, SBP, DBP and MAP showed significant decrease throughout the study period, as compared to Lignocaine group. The statistical analysis shows that, in Dexmedetomidine group, HR, SBP, DBP and MAP showed significant decrease throughout the study period, as compared to Lignocaine group. Conclusion: Newer agents like Dexmedetomidine, a centrally acting alpha-2 agonist suppresses reflex sympathetic stimulation caused by laryngoscopy & intubation more effectively than Lignocaine. Thus, it is concluded that Dexmeditoedine is a better drug compared to Lignocaine in attenuating pressure response to laryngoscopy & intubation.

Metrics of clonidine utilization in maintenance hemodialysis patients

Background: Clonidine is less frequently used by nephrologists. Data on clonidine prescribing trends in hemodialysis patients is sparse. We assessed the clonidine utilization metrics from the case records of patients undergoing maintenance hemodialysis.Methods: In this retrospective chart review, we analysed the clinical records of hemodialysis patients using clonidine. We evaluated the frequency of clonidine use, mean dose of clonidine and percentage of patients receiving a particular dose. Additionally, we also correlated dose of clonidine with anti-hypertensive pill count.Results: A total of 70 hemodialysis patients case records were screened. All 70/70 (100%) of them were hypertensive. Only 25/70 (35.74%) of patients were prescribed clonidine as an anti-hypertensive agent. The mean clonidine dose was 352±171 µg. Majority of patients 9/25 (36%) received 400 µg of clonidine. The dose of clonidine was prescribed in the order 400 µg (36%)>200 µg (32%)>600 µg (16%)>100 µg (8%)>300 µg (4%)=700 µg (4%). There was a statistically significant correlation in the strength of clonidine prescribed with increasing anti-hypertensive drugs (p<0.05).Conclusions: In our study, we observed that 80% of our hemodialysis patients were non responders to either systolic blood pressure or diastolic blood pressure or both. Oral clonidine use was observed in 35.74% of our hemodialysis patients. There was a linear trend showing an increased dose of clonidine with an increase in the anti-hypertensive pill count.

Oral premedication with pregabalin and clonidine for hemodynamic stability during laryngoscopy: A comparative study.

Background: Airway instrumentation of direct laryngoscopy and tracheal intubation are noxious stimuli that should be attenuated by appropriate premedication, smooth induction, and rapid intubation. The present study evaluated the clinical effi cacy of oral premedication with pregabalin or clonidine for attenuation of hemodynamic pressure response of airway instrumentation. The objective was to fi nd out the effi cacy of pregabalin and clonidine as an oral premedication and to observe hemodynamic stability during laryngoscopy. Methods: A total of 100 healthy patients aged 30-70 years with American Society of Anesthesiology Physical Status I and II of both gender, who met the inclusion criteria of general anesthesia, were randomly received pregabalin (150 mg) Group I or clonidine (100 μg) Group II, 60-70 mins before surgery as an oral premedication. Both groups were compared to pre-operative sedation, anxiety, heart rate (HR), and mean arterial pressure (MAP) at baseline, after premedication, induction, laryngoscopy, and extubation. Intraoperative analgesic drug requirement and any post-operative complication were recorded. Results: Incidence of hypotension and bradycardia were observed in 4% case in the clonidine group. Pre-operative sedation level was higher in the pregabalin group as compared to clonidine group. p>0.05 which shows there is no difference in both the drugs in terms of control of HR and MAP perioperatively. Both drugs are equally good to maintain hemodynamic stability during laryngoscopy. None of the patients has suffered from any post-operative side effects. Conclusion: Hemodynamic pressure response of airway instrumentation was attenuated with pregabalin and clonidine oral premedication without prolongation of recovery time and side effects.

Exaggerated blood pressure response during the exercise treadmill test as a risk factor for hypertension

Exaggerated blood pressure response (EBPR) during the exercise treadmill test (ETT) has been considered to be a risk factor for hypertension. The relationship of polymorphisms of the renin-angiotensin system gene with hypertension has not been established. Our objective was to evaluate whether EBPR during exercise is a clinical marker for hypertension. The study concerned a historical cohort of normotensive individuals. The exposed individuals were those who presented EBPR. At the end of the observation period (41.7 months = 3.5 years), the development of hypertension was analyzed within the two groups. Genetic polymorphisms and blood pressure behavior were assessed as independent variables, together with the classical risk factors for hypertension. The I/D gene polymorphism of the angiotensin-converting enzyme and M235T of angiotensinogen were ruled out as risk factors for hypertension. EBPR during ETT is not an independent influence on the chances of developing hypertension. No differences were observed between the hypertensive and normotensive individuals regarding gender (P = 0.655), skin color (P = 0.636), family history of hypertension (P = 0.225), diabetes mellitus (P = 0.285), or hypertriglyceridemia (P = 0.734). The risk of developing hypertension increased with increasing body mass index (BMI) and advancing age. The risk factors, which independently influenced the development of hypertension, were age and BMI. EBPR did not constitute an independent risk factor for hypertension and is probably a preclinical phase in the spectrum of normotension and hypertension.

Comparison of two doses of oral clonidine as a premedicant for attenuation of pressor response to laryngoscopy.

Background: The present study compared oral clonidine 0.3mg with 0.2 mg to attenuate hemodynamic response to laryngoscopy and intubation and also to evaluate the optimal dose of oral clonidine as premedication. Methods: A prospective, randomized, double blind trial performed on 40 patients of ASA Grade I & II, scheduled for planned ENT surgeries under general anaesthesia. Patients were divided into 2 groups depending on oral clonidine dose given 90 mins prior to induction. Group A received 0.3 mg while group B received 0.2 mg clonidine. Heart rate, SBP, DBP, MAP were monitored at various time intervals e.g. before premedication, before induction, at laryngoscopy, intubation, immediately after intubation and post intubation for 30 minutes. Patients were anesthetized with sodium thiopentone (2.5%) 5-7 mg/kg followed by suxamethonium 2 mg/kg i.v. Results: We observed a significant decrease in mean HR,SBP,DBP,MAP in both the groups (clonidine 0.2 and 0.3mg ) as compared to baseline and preinduction level. Tablet Clonidine 0.3 mg proved to be significantly effective in checking the rise in SBP. A highly significant (p < 0.01) fall in DBP was observed in Group A at 1, 3, 15, 30 mins post intubation as compared to Group B. At 3 min, 15 min and 30 min interval, highly significant (p <0.01) decrease in MAP observed with clonidine 0.3mg as compared to 0.2mg. In this study, no patient encounter complications like bradycardia, hypotension. Conclusions: Oral clonidine 0.3 mg premedication in adult patients 90 mins prior to induction is safe, convenient and more effective in suppressing the hemodynamic response to laryngoscopy & intubation as compared to clonidine 0.2 mg.

Drag reduction by polyethylene glycol in the tail arterial bed of normotensive and hypertensive rats

This study was designed to evaluate the effect of drag reducer polymers (DRP) on arteries from normotensive (Wistar) and spontaneously hypertensive rats (SHR). Polyethylene glycol (PEG 4000 at 5000 ppm) was perfused in the tail arterial bed with (E+) and without endothelium (E-) from male, adult Wistar (N = 14) and SHR (N = 13) animals under basal conditions (constant flow at 2.5 mL/min). In these preparations, flow-pressure curves (1.5 to 10 mL/min) were constructed before and 1 h after PEG 4000 perfusion. Afterwards, the tail arterial bed was fixed and the internal diameters of the arteries were then measured by microscopy and drag reduction was assessed based on the values of wall shear stress (WSS) by computational simulation. In Wistar and SHR groups, perfusion of PEG 4000 significantly reduced pulsatile pressure (Wistar/E+: 17.5 ± 2.8; SHR/E+: 16.3 ± 2.7 percent), WSS (Wistar/E+: 36; SHR/E+: 40 percent) and the flow-pressure response. The E- reduced the effects of PEG 4000 on arteries from both groups, suggesting that endothelial damage decreased the effect of PEG 4000 as a DRP. Moreover, the effects of PEG 4000 were more pronounced in the tail arterial bed from SHR compared to Wistar rats. In conclusion, these data demonstrated for the first time that PEG 4000 was more effective in reducing the pressure-flow response as well as WSS in the tail arterial bed of hypertensive than of normotensive rats and these effects were amplified by, but not dependent on, endothelial integrity. Thus, these results show an additional mechanism of action of this polymer besides its mechanical effect through the release and/or bioavailability of endothelial factors.

Diagnostic Value of Postexercise Systolic Blood Pressure Response for Detecting Coronary Artery Disease in Patients with Electrocardiographic Left Ventricular Hypertrophy / 中国医师杂志

Objective To investigate the diagnostic value of postexercise systolic blood pressure(SBP) response in detecting coronary artery disease(CAD) in patients with electrocardiographic left ventricular(LV) hypertrophy.Methods Acording to their results of selective coronary angiography,58 patients with electrocardiographic LV hypertrophy were divided into group 1(27 patients without significant coronary lesions) and group 2(31 patients with significant coronary lesions).Symptom-limited treadmill exercise testing was conducted in those patients.Results The SBP ratio(SBP at 3 minutes of recovery divided by SBP at peak exercise) was significantly higher in group 2 than in group 1(0 98?0 11 vs 0 84?0 11,P

Relationship between Exercise-induced Blood Pressure Response and Left Ventricular Hypertrophy in Patients with Hypertension

BACKGROUND: In hypertensive patients, who show abnormal blood pressure(BP) response during exercise, more excessive blood pressure response may occur in the daily life, and cause end organ damage. However, previous studies about exaggerated BP response during exercise were not enough to investigate its significance and role in left ventricular hypertrophy. The purpose of this study was to determine the relation between exaggerated BP response during exercise and left ventricular hypertrophy. METHODS: The treadmill exercise test and echocardiography were performed in 117 patients with hypertension. Sixty six patients showed normal BP response, fifty one patients showed exaggerated BP response. Exaggerated BP response was defined as elevation of peak exercise systolic BP over 210 mmHg or >10 mmHg elevation of peak exercise diastolic BP from baseline. The correlation between BP response and left ventricular mass index were evaluated in two groups. RESULT: The results were as follows; 1. The peak systolic and diastolic BP were significantly higher in patients with exaggerated BP response than that in patients with normal BP response (p<0.05). 2. There was weakly significant relation between peak exercise systolic BP and left ventricular hypertrophy, but diastolic BP showed no significant correlation with left ventricular hypertrophy. 3. The left ventricular mass index was significantly increased in patients with exaggerated BP response (normal BP response: 12025 gm/m2, exaggerated BP response: 16946 gm/m2 , p=0.04). CONCLUSION: These results indicate that, as compared with resting BP, exercise BP response seems to be important in the treatment of hypertension and more strict blood pressure control may be needed in hypertensive patients with exaggerated BP response. Further study is needed to understand the significance of exaggerated BP response in hypertension.

The Effect of Indomethacin on Biphasic Intraocular Pressure Response to Laser Irradiaion of the Iris

Laser irradiation of the iris can induce acute increase in intraocular pressure (IOP) as well as hypotony. the author evaluated the effect of the prostaglandin on the biphasic IOP response. Of 14 animals, 7 experimental eyes were treated with topical indomethacin(indomethacin group) and 7 experimental eyes received topical saline(no indomethacin group) prior to laser photocoagulation, and the contralateral eyes were used as control eyes. Change in IOP was defined as [IOP of the experimental eye-IOP of the control eye]. Mean change in IOP reached its highest level 1 hour after laser treatment and subsequently decreased in the no indomethacin group(p=<0.0001, repeated measures ANOVA).However, indomethacin pretreatment showed no statistically significant changes throughtout the experimental period as compared with the baseline value(p=0.4, repeated measures ANOVA). Since indomethacin is known to be a potent ingibitor of prostaglandin synthase, our trsults suggest that prostaglandin plays a role on the biphasic IOP change.

Relationship between Pressure Response to Repeated Elevation of Intracranial Pressure and Central alpha-Adrenoceptor in Rabbit

It is well documented that elevation of intracranial pressure is accompanied by arterial blood pressure(cushing response) in laboratory animals as well as in human. When the elevation of intracranial pressure(ICP) was repeated in a rabbit at an interval of 30-60 min, the blood pressure increased more promtly than in the first elevation of ICP, suggesting that mechanism involved in the pressure might be different. Therefore, this study was undertaken to clarify the pharmacological characteristics of the response to the first and repeated(second) elevation of ICP in urethane anesthetized rabbits. Increasing ICP, induced by infusion of saline into a ballooned in the epidural space, produced arise of the arterial blood pressure. When the blood pressure reached a peak, the balloon was suddenly deflated to reduced the ICP and blood pressure declined (the first ICP elevation experiment). After 30-60 min the same procedure was repeated (the second ICP-elevation experiment) Results are summarized as follows; 1) In the first ICP elevation experiment, the arise of ICP was relatively slow at the beginning of the infusion but became sharp as the infusion proceeded. When ICP increased sharply BP also increased abruptly and heart rate decreased. 2) In the second ICP elevation experiment, the slight decrease in BP which appeard at the beginning of the first ICP elevation experiment rat observed, so that only an abrupt arise of BP was seen. 3) Intravenous chlorisondamine inhibited the pressure responses in the second ICP elevation experiment. 4) Intraventricular corynanthine had little effect on the pressure response to the first ICP elevation but inhibited the pressure response to the second ICP elevation. 5) Intraventricular clonidine, yohimbine and prazosin little effect on the pressure response to the second ICP elevation. From this results that functional integrity of central alpha 2-adrenoceptor which took part in the pressure response to the first ICP elevation might have deranged in the second ICP elevation and that central alpha 1-adrenoceptors play a dominant role in the pressure response to the second ICP elevation.

Relationship between Central alpha2-Adrenoceptors and Pressor Response to Raised Intracranial Pressure in Rabbits

The effects of intraventricular alpha2-adrenoceptor agonist and antagonist, clonidine and rauwolscine, on changes of blood pressure induced by the rise of intracranial pressure were investigated in urethane-anesthetized rabbits. 2) The rise of ICP, induced by the infusion of saline into a balloon placed in the epidural space, was comparatively slow in the beginning of the infusion but became sharp as the infusion proceeded. Corresponding with the gradual increase of ICP, there was a slight decrease in BP. An abrupt rise of BP was observed when ICP showed a sharp increase. 3) Intraventricular rauwolscine 5(microgram) by itself did not affect BP. In these rauwolscine-treated rabbits the increase of both ICP and BP by the infusion was similar to that of the control animals. 4) The pretreatment with rauwolscine 50(microgram) did hardly affect BP, but this made the increase of ICP and BP by the infusion different from that of the control animals. The slight hypotensive response in the beginning of the infusion did not appear and the pressor response to the raised ICP was markedly facilitated. The volume of saline inused into the infusing balloon to cause the same increase of ICP as in the control animals was much smaller than in the control ones, and the magnitude of the maximal increase of BP was much greater. 5) The pretreatment with 500 microgram of intraventricular rauwolscine produced an increase of BP. In these animals the increase of both ICP and BP by the infusion seemed to be slightly facilitated than in the control animals. 6) Intraventricular clonidine 30(microgram) markedly decreased BP. In these clonidine-treated animals the slight hypotensive response in the beginning was more distinct than in the control animals, and the pressor response was hardly seen. 7) The hypotensive response to intraventricular clonidine 30(microgram) was weakened in the animals pretreated with intraventricular rauwolscine 500(microgram). In these animals the increase of both ICP and BP by the infusion appeared as in the control animals. 8) The above results suggest that the pressor response to the raised ICP in rabbits was inhibited under the condition of stimulation of central alpha2-adrenoceptors and facilitated under the condition of blockade of the receptors. It seems that the rise of blood pressure takes place when the activity of alpha2-adrenoceptors is impared by the increased pressure of the balloon placed in the epidural space.