Effects of concentrated ambient particles on heart rate, blood pressure, and cardiac contractility in spontaneously hypertensive rats during a dust storm event

Epidemiological studies have suggested that cardiovascular mortality and morbidity increased during Asian dust events. The findings were still inconclusive though. We have shown an increased pulmonary toxicity in diseased animals during a dust storm event. However, the toxicity nature of dust storm particles remains unclear. It is our objective in this study to further investigate the cardiovascular effects of concentrated PM(2.5) on spontaneously hypertensive rats during the same dust storm event. Four spontaneously hypertensive rats were implanted with radiotelemetry transmitters at the age of 10 wk. Baseline heart rate, mean blood pressure, and cardiac contractility (measured as QA interval, QAI) data were collected 4 wk before. Exposure group received concentrated ambient particles inhalation for 6 h during a dust storm event, while the control group received room air inhalation at the same time. Self-control data were collected 4 wk after the event during the same clock hours while there was no dust storm. Gravimetric analysis showed a particle mass concentration of 315.55 microg/m(3) during the 6 h of exposure. A linear mixed-effects model revealed sigmoid increases in heart rate (to a maximum of 93.8 +/- 18.8 bpm) and mean blood pressure (to a maximum of 14.8 +/- 5.4 mm Hg), and a sigmoid decrease of QAI (to a maximum of - 3.5 +/- 1.5 ms) during the exposure after an initial incubation period. We conclude that concentrated dust storm particles, which are different from products of automobile combustion process, may cause adverse cardiovascular effects on diseased animals.     

Gender differences in blood pressure and heart rate in spontaneously hypertensive and Wistar-Kyoto rats

1. In general, premenopausal women are known to have lower blood pressure than men and animal models have shown a similar sexual dimorphism. However, many studies in animals have been performed using anaesthetized or restrained models. Current experiments were conducted to investigate the relationships among resting heart rate, blood pressure and gender in conscious, unrestrained normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). 2. Biotelemetry transmitters were implanted in 6-month-old animals. Values for heart rate, diastolic blood pressure, systolic blood pressure and pulse pressure were recorded continuously at 10 min intervals after all animals recovered completely from surgery. 3. Normal circadian rhythms in heart rate were found in all rats, with no significant differences among the four groups; the circadian variation in blood pressure was evident in all groups, although much smaller. Heart rate was found to be higher in WKY female rats than in the other three groups. Male WKY rats, male SHR and female SHR had similar heart rates. Male SHR had significantly higher systolic and diastolic blood pressures than female SHR. Male and female WKY rats had similar diastolic blood pressure, but males had slightly higher systolic pressure than females. No significant difference in pulse pressure was found in WKY male and female rats. Male SHR showed significantly higher pulse pressure than female SHR at most times during the day. 4. In conclusion, these results indicate that hypertension is exacerbated in male SHR compared with females under conscious resting conditions and demonstrate that the higher heart rate observed in WKY female rats is not present in the SHR model.     

Cardiopulmonary responses in spontaneously hypertensive and Wistar-Kyoto rats exposed to concentrated ambient particles from Detroit,Michigan

Toxicological effects have been observed in rats exposed to concentrated ambient particles (CAPs) from different regions of the United States. The objective of this study was to evaluate the cardiopulmonary and systemic effects of CAPs in Detroit. The authors stationed a mobile concentrator at a location near major traffic and industrial sources. Spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) rats were exposed to fine CAPs (diameter <?0.1–2.5?μm) 8?h/day for 13 consecutive days. Animals were implanted with telemeters, and electrocardiogram data were recorded continuously. Bronchoalveolar lavage (BAL) fluid and plasma were analyzed. Comprehensive exposure monitoring was conducted, including CAPs components. CAPs exposure concentrations were 103–918?μg/m³ (mean?=?502?μg/m³). The authors found no statistically significant differences in heart rate or SDNN (standard deviation of the normal-to-normal intervals), a measure of heart rate variability, between CAPs-exposed and control rats. The authors found significantly higher levels of C-reactive protein in the serum of CAPs-exposed SH rats compared with air-exposed animals. Protein in BAL fluid was elevated in WKY rats exposed to CAPs. Measurement of trace metals in lung tissue showed elevated concentrations of V, Sb, La, and Ce in CAPs-exposed SH animals versus controls. These elements are generally associated with oil combustion, oil refining, waste incineration, and traffic. Examination of wind rose data from the exposure period confirmed that the predominant wind direction was SSW, the direction of many of the aforementioned sources. These results indicate that ambient particles in Detroit can cause mild pulmonary and systemic changes in rats, and suggest the importance of local PM_2.5 sources in these effects.     

Effects of vasopressin and V1 receptors blockade on blood pressure and heart rate in spontaneously hypertensive rats.

The aim of the present study was to compare effects of intravenous infusion of vasopressin AVP and V1 receptors blockade on blood pressure and heart rate in normotensive (WKY) and spontaneously hypertensive (SHR) rats. A 20 min vasopressin infusion (1.2 ng/kg/min) elicited significantly greater increase in mean blood pressure (MP) in SHR than in WKY. Heart rate was significantly reduced in SHR while nonsignificantly in WKY. A 20 min dEt2 AVP (V1 antagonist) infusion (0.5 microgram/kg/min) elicited significant decrease in MP and increase in heart rate (HR) in SHR, but produced no effect in WKY. The data indicate that SHR are more susceptible to pressor and hypotensive effects of sustained elevation of AVP and AVP antagonist. The results support the hypothesis that AVP may contribute to pathogenesis of hypertension.     

Effects of verapamil on blood pressure and heart rate in neurogenic hypertensive rats

The mechanism(s) underlying the prolactin (PRL)-releasing effect of benserazide (Bz), a peripheral inhibitor of L-aromatic amino-acid decarboxylase, was investigated in the rat. In intact male and female rats, Bz was ineffective to increase significantly plasma PRL at 0.8 mg/kg i.p. but elicited an already maximal effect at 1.6 mg/kg. Bz added to in vitro incubated anterior pituitaries (APs) did not alter PRL secretion at the dose of 3.8 X 10(-6)M but increased PRL release at 10(-4)M. Bz, even at very high doses (up to 10(-3) M), did not displace [3H]spiroperidol binding from AP membrane preparations. In rats having had mechanical ablation of the medio basal hypothalamus (MBH), Bz (15 mg/kg i.p.) induced no rise in plasma PRL and did not counteract the striking inhibitory effect of a dopamine (DA) infusion (5 micrograms/kg per min per 120 min). Administration of Bz (15 mg/kg i.p.) into intact male rats decreased significantly the DA concentrations in the median eminence (ME) but not in the residual hypothalamus and the AP. In the same rats 1-dopa (50 mg/kg i.p.) increased significantly the DA concentrations not only in the ME but also in the hypothalamus and the AP. Bz given concurrently with 1-dopa markedly reduced the rise in DA concentrations induced by 1-dopa in the ME, and greatly potentiated the increase in DA concentrations in the hypothalamus. These data indicate that the mechanism whereby a single administration of Bz increases PRL secretion in the rat is not consistent with the postulated DA receptor antagonist action of the drug, but instead implies inhibition of the decarboxylation of 1-dopa at dopaminergic nerve terminals of the ME.     

Effects of concentrated ambient particles on airway responsiveness and pulmonary inflammation in pulmonary hypertensive rats

Epidemiological studies have associated particulate air pollution with exacerbation of lung function in human populations. However, the relationship between ambient particles and lung function in animal studies has been inconsistent. In order to investigate the effects of concentrated ambient particles (CAPs) on airway responsiveness, we exposed pulmonary hypertensive rats to CAPs using particle concentrator at an EPA of Taiwan supersite, located at a traffic busy urban area nearing Taipei city. The exposure group (n = 5) was exposed to CAPs for 6 h each day for 3 consecutive days (mean mass concentration = 371.7 microg/m(3)), while a control group (n = 6) was exposed to HEPA-filtered air. Whole-body barometric plethysmography was used to measure respiratory frequency, tidal volume, and airway responsiveness before and after exposure. Enhanced pause (Penh) was used as an indicator of airway responsiveness. To improve the accuracy of airway responsiveness measurement, we controlled temperature and humidity. Further, airway responsiveness was determined 5 h after particle exposure to overcome the stress effect in nose-only exposure chambers. After CAPs exposure, we found decreased respiratory frequency and increased tidal volume (p < .05). Using the methacholine challenge test, a significant difference of Penh measured before and after experiment was observed in the CAPs group (p < .05), but not in the filtered air group. Further analysis showed that the Penh difference before and after exposure in the CAPs group was significantly greater than that in the filtered air group (p < .05). We conclude that CAPs could induce airway hyperresponsiveness in pulmonary hypertensive rats.     

Nicardipine decreases blood pressure and heart rate at nucleus tractus solitarii of spontaneously hypertensive rats

The effects of the dihydropyridine (DHP) calcium channel antagonist, nicardipine, on central cardiovascular regulation were investigated by injecting it into the cisterna magna or directly into the nucleus tractus solitarii (NTS), in anesthetized normotensive or spontaneously hypertensive (SHR) rats. Intracisternal injections of nicardipine (1-10 micrograms/kg) dose-dependently decreased blood pressure in SHR; there was no significant change in cardiovascular parameters in normotensive rats. In SHR, nicardipine (100 ng) microinjected bilaterally into the NTS produced hypotension and bradycardia. The same doses of nicardipine intravenously injected did not change either parameter. Previous administration of the beta-adrenoceptor blocking drug, tertatolol (50 micrograms/kg i.v.), prevented the nicardipine-induced bradycardia and hypotension after injection into the NTS. These data suggest that part of the central cardiovascular effects of nicardipine result from an interaction with DHP sites within the NTS leading to a withdrawal of the sympathetic tone.     

Effects of benidipine hydrochloride (Coniel) on blood pressure, heart rate and plasma norepinephrine concentration in spontaneously hypertensive rats]

We investigated the effects of benidipine hydrochloride (benidipine, Coniel) on blood pressure, heart rate and plasma norepinephrine (NE) concentration in spontaneously hypertensive rats and compared them with those of other calcium channel blockers. Benidipine (2 mg/kg, p.o.) was compared with the equihypotensive doses of nifedipine (5 mg/kg), cilnidipine (6 mg/kg) and amlodipine (3 mg/kg). All the 4 calcium channel blockers exhibited significant antihypertensive effects. Nifedipine and cilinidipine significantly increased heart rate, as compared with that in the control group, whereas benidipine or amlodipine did not significantly affect it. The area under the curves for hypotensive effect and tachycardic effect for 10 hr after the drug administration were compared among the 4 compounds. As a result, the tachycardic effect of benidipine was significantly lower than those of nifedipine, cilnidipine and amlodipine, while the hypotensive effects were similar among the 4 compounds. Nifedipine and amlodipine, significantly increased plasma NE concentration, cilnidipine tended to increase it. In contrast, benidipine did not significantly affect plasma NE concentration. These results suggest that the effects of benidipine on plasma NE concentration and heart rate are less prominent than those of the other calcium channel blockers.     

Effects of nifedipine on blood pressure and heart rate in conscious neurogenic hypertensive rats

The effects of nifedipine (15 micrograms/kg, i.v.) on mean blood pressure (MBP) and heart rate were studied in neurogenic hypertensive rats (NHR), compared with renovascular hypertensive (RHR), and control (CR) rats. The maximal MBP reduction reached 32, 37 and 9%, respectively. The baseline MBP was recovered after 120, 150, and 5 min, respectively. The hypotension was not accompanied by changes in the baseline high heart rate of NHR and by tachycardia in CR and RHR groups. The data show the antihypertensive efficacy of nifedipine in both models of hypertension and indicate that under conditions of increased sympathetic tone the cardiac pacemaker cannot be easily inhibited by nifedipine.     

Effect of prolyl-leucyl-glycinamide on blood pressure, heart rate and angiotensin converting enzyme activity in spontaneously hypertensive and Wistar-Kyoto normotensive rats

The effect of melanotropin release inhibiting factor (L-prolyl-L-leucyl-glycinamide, MIF) on blood pressure and heart rate of both spontaneously hypertensive (SH) and age-matched normotensive Wistar-Kyoto (WKY) rats was investigated. A single s.c. injection of MIF at a lower dose (1 mg/kg) had no effect on the blood pressure of either SH or WKY rats when measured 1,4 and 7 hr after the injection of MIF. Higher doses of MIF (2 or 4 mg/kg), on the other hand, significantly depressed blood pressure in SH animals at 4 and 7 hr after the drug injection. However, MIF had no effect on the blood pressure of WKY rats. None of the doses of MIF had any appreciable effect on the heart rate of either SH or WKY rats. Angiotensin-converting enzyme (ACE) activity of anterior pituitary of WKY rats was significantly higher than that of SH rats. ACE activity of neurohypophysis, however, was lower in WKY rats than in SH rats. No change in the ACE activities of central and peripheral tissues (plasma, pituitary, striatum and hypothalamus) of SH rats was observed 4 hr after the administration of MIF (1, 2 or 4 mg/kg), a time at which MIF produced significant antihypertensive effect. It is concluded that MIF causes a delayed lowering of blood pressure only in the genetically hypertensive rats and that this effect is not mediated via an action on the ACE.     

Qi盐对肾性和自发性高血压大鼠血压的影响

目的观察Qi盐对肾性和自发性高血压大鼠(SHR)的降压作用.方法通过缩窄左肾动脉而制备2K1C夹的肾性高血压模型,同时选用16周龄的SHR,2种实验鼠均连续给予Qi盐0.4、0.2、0.1 g·kg-1,14 d(ig,qd),观察其对肾性和SHR BP的影响.结果Qi盐各剂量组及普通盐组对肾性高血压模型鼠BP在用药d 7、14均无明显的影响,而对SHR,Qi盐0.4、0.2 g·kg-1给药7d后可显著降低BP,与对照组相比,P<0.05,但14 d后BP有所回升.结论Qi盐对肾性高血压模型无明显的治疗作用,但在给药7 d后能显著地降低SHR的BP.     

Effects of BDF 9198 on left ventricular contractility in advanced spontaneously hypertensive rats with heart failure

In the first part of this study, we characterized 24-month-old Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs), their heart weights, and the responses of the isolated left ventricles to electrical stimulation. In the main part of the study, we tested whether the positive inotropic effects of BDF 9198, which prevents the closure of the cardiac sodium channel, were present in senescence and heart failure. Thus, we studied the effects of BDF 9198 on the left ventricle strips of 24-month-old WKy rats (senescence) and SHRs using contractility methods. In comparison with WKY rats, the left ventricles of 24-month-old SHRs were hypertrophied and had prolonged times to peak contraction. BDF 9198 (10(-8) to 10(-6) M) was a positive inotrope on the left ventricles of WKY rats, with a maximum augmenting effect of 122% with BDF 9198 at 10(-7) M. The magnitude of the augmenting effects of BDF 9198 were reduced in SHR heart failure, with a maximum augmenting effect of 26% at 10(-7) M. BDF 9198 at 10(-6) M attenuated the responses of the SHR left ventricle to electrical stimulation. In conclusion, the potential of drugs that prevent closure of the sodium channel as positive inotropes in the treatment of heart failure should be further considered.     

Modification of circadian blood pressure and heart rate variability by five different antihypertensive agents in spontaneously hypertensive rats.

Effects of captopril, clonidine, hydralazine, metoprolol, and prazosin on the circadian variability of blood pressure (BP) and heart rate (HR) as well as on BP and HR rises at awakening were studied in spontaneously hypertensive rats (SHR). An on-line computerized system was used for continuous intraarterial (i.a.) recording of BP and HR. Drugs were infused intravenously (i.v.) with osmotic minipumps. Circadian BP patterns were more pronounced and variable in SHR than in Wistar-Kyoto normotensive control rats. HR patterns were similar in both groups. Antihypertensive treatment resulted in differential effects on the expression of the circadian BP and HR patterns in SHR. Reductions in BP variability and reductions in the awakening increase in BP were not correlated with the BP-lowering efficacy of agents. Treatment with clonidine reduced both circadian variability of BP and HR and the awakening increase. Prazosin reduced circadian BP variability and its awakening increase, whereas metoprolol reduced circadian HR variability only. Hydralazine and captopril did not cause any major effects on the circadian variability of BP and HR. These data indicate that circadian rhythms of BP and HR are under sympathetic control in SHR and are not influenced by nonsympatholytic vasodilators.     

Effects of phentolamine,dihydroergocristine and isoxsuprine on the blood pressure and heart rate in normotensive,hypotensive and hypertensive rats

Summary Phentolamine, dihydroergocristine and isoxsuprine were compared for their effects on the blood pressure in anaesthetized normotensive rats, in rats made hypotensive by ganglionic blockade or by pithing and in rats with noradrenaline-induced hypertension. Their ability to inhibit pressor responses elicited by electrical stimulation of the posterior hypothalamus and of the sympathetic outflow from the spinal cord was also investigated.All three drugs appeared very potent in inhibiting noradrenaline-induced hypertension and caused a dose-dependent fall in blood pressure in normotensive rats, which however was less pronounced with dihydroergocristine than with phentolamine and isoxsuprine. In hypotensive rats, dihydroergocristine caused a rise in blood pressure.At higher doses than those required to block noradrenaline-induced hypertension, the three drugs inhibited pressor responses elicited by electrical stimulation and were equally active on peripherally- and centrally-evoked responses.Simultaneous recording of heart rate and blood pressure, both in anaesthetized and in pithed rats, indicated a reflex origin for phentolamine-induced tachycardia and a direct cardiac stimulation for isoxsuprine. Reflex changes of heart rate were not observed with dihydroergocristine.     

Effects of the vasodilator endralazine given with the antihypertensive agent guanfacine on heart rate and blood pressure of spontaneously hypertensive rats and normotensive dogs

Endralazine (BQ 22-708, Miretilan) and guanfacine (BS 100-141, Estulic) were tested alone and in combination for their effects on blood pressure and heart rate in conscious spontaneously hypertensive rats and conscious normotensive dogs. During combined administration of endralazine and guanfacine to spontaneously hypertensive rats, guanfacine 1 mg kg-1 i.v. blocked the tachycardia caused by endralazine, 1 mg kg-1 i.v. After oral administration, the tachycardia induced by 0.5 and 1 mg kg-1 of endralazine was inhibited dose-dependently by 0.05, 0.1 and 0.5 mg kg-1 of guanfacine. The antihypertensive efficacy of endralazine was either unchanged or increased by guanfacine at 0.05-1 mg kg-1. In normotensive conscious dogs, 0.2 mg kg-1 i.v. of guanfacine antagonised the tachycardia elicited by 0.3 mg kg-1 i.v. of endralazine. The elimination of the endralazine-induced reflex tachycardia by guanfacine suggests that the combination of both drugs could be useful in antihypertensive therapy.     

Disturbance of circadian rhythm in heart rate, blood pressure and locomotive activity at the stroke-onset in malignant stroke-prone spontaneously hypertensive rats

Malignant stroke-prone spontaneously hypertensive rats (M-SHRSP), separated from SHRSP, develop severe hypertension and spontaneously develop stroke at early ages. Using this model of cerebrovascular stroke, influence of stroke-onset on the autonomic nervous system was investigated. Heart rate (HR), systolic and diastolic blood pressures (SBP and DBP) and locomotive activity were monitored during development of stroke using a telemetry system. Stroke-onset was assessed by neurologic symptoms, changes in body weight, fluid intake and serum NOx level. The rat displayed a nocturnal pattern of circadian rhythms. At stroke-onset, mean HR over 24 h increased by 20 to 30 bpm and rapidly increased at post stroke, approximately 100 bpm higher than that at pre stroke. Circadian variation in HR, which was normally 50 bpm higher during night than during day, attenuated at stroke-onset, and it was blunted or reversed at post stroke. BP variation, which was approximately 7 mmHg higher at night than at day, decreased one or two days before stroke-onset and reversed at post stroke, especially in DBP. Insufficient falls in HR and BP during the day mainly accounted for the disturbed circadian variations. Variation of locomotive activity also decreased. These changes serve as reliable and accurate markers for stroke-onset in evaluation of drugs for the prevention and outcome predictions of stroke.     

Ketanserin stabilizes blood pressure in conscious spontaneously hypertensive rats

1. It has been demonstrated that blood pressure variability (BPV) is increased in hypertension and related to organ damage. It will be important to lower BPV in the treatment of hypertension. The present study was designed to investigate the effect of ketanserin, a 5-HT2A receptor antagonist with a weak alpha1-adrenoceptor blocking effect, on BPV in conscious spontaneously hypertensive rats (SHR). 2. It was found that ketanserin decreased blood pressure (BP) and BPV in SHR when administered intravenously (3 mg/kg, i.v.). Ketanserin decreased BPV, but not the BP level, when administered intracerebroventricularly (50 microg/rat, i.c.v.). 3. Prazosin, an alpha1-adrenoceptor antagonist, lowered BP but did not affect BPV when given either i.v. (0.5 mg/kg) or i.c.v. (30 microg/rat). Ritanserin (0.625 mg/kg, i.v.; 40 microg/rat, i.c.v.), a 5-HT2A receptor antagonist, decreased BPV only when administered i.c.v. and did not modify the BP level. 4. Ketanserin enhanced arterial baroreflex function in SHR when given either i.v. or i.c.v. 5. The stabilizing effect of ketanserin on BP was persistent when administered intragastrically. This administration route is similar to oral administration clinically. 6. It is concluded that ketanserin is an antihypertensive agent with an effect of reducing BPV. This effect is mainly mediated by central 5-HT2A receptors and is probably attributable to the restoration of arterial baroreflex function.     

Effects of potassium supplementation on blood pressure, electrolytes and 3H-norepinephrine release in spontaneously hypertensive rats

Potassium supplementation has been shown to decrease blood pressure in human and animal models of hypertension. The purpose of this study was to determine if potassium supplementation altered sympathetic nerve activity by altering 3H-norepinephrine release in caudal artery preparations of spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Supplementation in the drinking water with 0.5 or 1.0% KCl for 5 weeks lowered blood pressure (19 and 25 mm Hg, respectively) in SHR but had no effect on WKY. The decrease in blood pressure with 0.5% KCl was not accompanied by significant changes in either plasma or cerebrospinal fluid (CSF) sodium or potassium levels in either SHR or WKY. 3H-Norepinephrine release induced by 56 mmol/l KCl was not altered in either SHR or WKY. However, the ability of yohimbine to enhance 3H-norepinephrine release in caudal artery preparations was significantly decreased by potassium supplementation in SHR, but was not affected in WKY. These data suggest that potassium supplementation may alter alpha 2-adrenoceptor activity. Further studies are required to determine if this altered alpha 2-adrenoceptor activity plays a direct role in the blood-pressure-lowering effects of potassium supplementation.