Clinical and Experimental Pharmacology and Physiology (1992) 19,833-838
EFFECTS OF NOISE ON BLOOD PRESSURE AND VASCULAR REACTIVITIES Chin-Chen Wu, Shiu-Jen Chen and Mao-Hsiung Yen Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan (Received 27 April 1992; revision received 5 August 1992)
SUMMARY 1. The present study investigated the effects of noise stress (100 dB, 1 kHz, 4 h/day, 6 days/week) on both systolic blood pressure and vascular reactivities in rats exposed to noise for 2 and 4 weeks. The systolic blood pressure was significantly increased after rats were exposed to noise for 4 weeks but not 2 weeks. 2. In isolated thoracic aortic rings, the responses to serotonin were enhanced in noise-treated rats while there were no changes in response to phenylephrine and high K' between noise-treated and control rats. 3. The relaxant responses to endothelium-dependent vasodilators (A23 187 and acetylcholine) in noise-treated rats were less than those in control rats. The vasodilator responses to acetylcholine were completely abolished by methylene blue or NW-nitro-L-arginine. 4. Responses to the endothelium-independent vasodilator, nitroglycerin, were not significantly changed after rats were exposed to noise. 5. The enhanced response to vasoconstrictors and the attenuation to endothelium-dependent vasodilators may account for elevations in blood pressure during noise stress. This indicates that the elevation in blood pressure by noise stress may be partly due to the deterioration of endothelial function. Key words: A23187, acetylcholine, endothelium, high K+, nitroglycerin, noise, phenylephrine, serotonin.
INTRODUCTION Noise has been recognized as an environmental hazard with the potential for inducing chemical and physiological disturbances of the endocrine, cardiovascular and nervous systems, in addition to its effects on audition (Leake 1970). Several investigators have reported a relationship between noise exposure and elevated peripheral resistance and thus blood pressure in humans (Jonsson & Hansson 1977; Andren et al. 1979). Investigations with rats have also indicated that noise exposure may contribute to elevated blood
pressure (Medoff & Bongiovanni 1945; Yeakel et al. 1948; Borg 1978a, b, c). Since it is known that noise exposure of a short duration significantly alters blood pressure, heart rate and peripheral vascular tone, the cardiovascular system has been chosen as a model. Recently, many reports reveal that the vascular endothelium plays an important role in many cardiovascular diseases, such as hypertension, stroke and atherosclerosis (Konishi & Su 1983; Lockette et al. 1986; Bossaier et a/. 1987;
Correspondence: Chin-Chen Wu, Department of Pharmacology, National Defense Medical Center, Taipei P.O. Box 90048-504, Taiwan.
834
C-C. Wu et al.
Rosenblum et al. 1987; Yamamoto et al. 1988; Rosenblum et al. 1989). The mechanism(s) by which noise exposure may lead to elevations in blood pressure and the effect of noise exposure on vascular reactivity have not been fully elucidated. One possibility is that noise may alter the function of the vascular endothelium, which may in turn elevate blood pressure by increasing vascular resistance. This hypothesis was evaluated by investigating the effects of noise on in virro vascular reactivities and by exploring the possible role of the endothelium in the relationship between noise and elevations in blood pressure.
METHODS Male Sprague-Dawley rats (220-250 g) were exposed to noise in Plexiglas cylindrical cages. The rats had sufficient room to move freely inside the cages. A loudspeaker (Speaderlab, WA, USA; Model KR4580) was mounted 30 cm above the cage and activated by a white noise generator (Lehigh Valley Electronics, USA; Model 581-02) powered by an amplifier system (HewlettPackard, CA, USA; 467A power amplifier and 6215A power supply). The frequency range of the noise generated was up to 1 kHz. Noise intensity was measured with a sound meter (B&K Inc, IL, USA.) and found to be uniform inside the cage. In each experiment, rats were exposed to white noise at 100 dB for 4 h per day, 6 days per week for 2 or 4 weeks. Control animals were sham-exposed (i.e. they were placed in the exposure cage and exposed to the ambient noise for the same exposure cage from 8:30 h to 12:30 h. At the end of the exposure period, rats were returned to the home cage and sacrificed 24 h later. Blood pressures were measured by the tail-cuff method and taken before rats were exposed to the noise and at 2 week intervals. The measurement of blood pressure was made at around 8:OO h. Before rats were sacrificed, they were anaesthetized with urethane (1.2 g/ kg, i.p.) and thoracic aortas were cut from control and noise-treated rats. These preparations were immediately placed in a cold physiological salt solution (PSS) of the following composition (mmol/ L): NaCl 118, KCI 4.7, NaHCO3 25, KH2P04 1.2, MgC12 1.25, CaCl2 2.5 and glucose 11. The connective tissue around the blood vessels was removed. Each segment of the vessels was cut into rings about 4 mm in length. Care was taken to preserve the endothelium of the vascular rings. The rings were suspended in a tissue bath containing 20 mL PSS (37°C) bubbled with a mixture of 95% 0 2 and 5% COz, and connected to Grass FT03C force transducers. The changes of vascular tension were recorded iso-
metrically on a Grass Model 7D polygraph. All preparations were equilibrated for 60-90 min under a resting tension of 3.0 g, which was the optimal tension for the aortic rings of both rats. After the equilibration period, a submaximal vasoconstriction was elicited with phenylephrine (0.3 pmol/ L) on the aortic rings. Then, acetylcholine (ACh; 1.0 pmol/ L) was added for 5 min to determine whether the endothelium had been mechanically injured. This procedure was repeated once in each preparation. Drugs were then removed from the bath by several washes with PSS and the rings were allowed to relax to study vascular reactivities in a cumulative manner. In relaxation studies, the rings were precontracted with phenylephrine (0.3 pmol/ L). After the contraction had reached a steady state, the vasodilators were added to the tissue bath in a cumulative manner. The vessels were then incubated for 10min with Nu-nitro+ arginine (50 pmol/L; Ishii et al. 1990) or methylene blue (10 pmol/L; Martin et al. 1985), and the experiment of ACh-induced relaxations was repeated. If the inhibitors by themselves induced an increase in tension or potentiated the contraction evoked by phenylephrine, the added concentration of phenylephnne was adjusted to match the level of contraction reached in the corresponding control experiment.
Chemicals Drugs used in this study were phenylephrine HC1 (Sigma Chemical Co., St. Louis, MO, USA), 5hydroxytryptamine (serotonin) creatinine sulfate (Sigma), acetylcholine chloride (Sigma), calcium ionophore A23 187 (Sigma), nitroglycerin (American Critical Care, American Hospital Supply Co., McGaw Park, IL, USA), NW-nitro-L-arginine methylester (Sigma) and methylene blue (Sigma). All concentrations are expressed as final molar concentrations in the tissue bath.
Statistical analysis
*
Data are reported as mean s.e.m. Statistical evaluation was performed using multiple comparison (Dunnett) following one-way analysis of variance (ANOVA). A value of P
EFFECTS OF NOISE ON BLOOD PRESSURE AND VASCULAR REACTIVITIES Chin-Chen Wu, Shiu-Jen Chen and Mao-Hsiung Yen Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan (Received 27 April 1992; revision received 5 August 1992)
SUMMARY 1. The present study investigated the effects of noise stress (100 dB, 1 kHz, 4 h/day, 6 days/week) on both systolic blood pressure and vascular reactivities in rats exposed to noise for 2 and 4 weeks. The systolic blood pressure was significantly increased after rats were exposed to noise for 4 weeks but not 2 weeks. 2. In isolated thoracic aortic rings, the responses to serotonin were enhanced in noise-treated rats while there were no changes in response to phenylephrine and high K' between noise-treated and control rats. 3. The relaxant responses to endothelium-dependent vasodilators (A23 187 and acetylcholine) in noise-treated rats were less than those in control rats. The vasodilator responses to acetylcholine were completely abolished by methylene blue or NW-nitro-L-arginine. 4. Responses to the endothelium-independent vasodilator, nitroglycerin, were not significantly changed after rats were exposed to noise. 5. The enhanced response to vasoconstrictors and the attenuation to endothelium-dependent vasodilators may account for elevations in blood pressure during noise stress. This indicates that the elevation in blood pressure by noise stress may be partly due to the deterioration of endothelial function. Key words: A23187, acetylcholine, endothelium, high K+, nitroglycerin, noise, phenylephrine, serotonin.
INTRODUCTION Noise has been recognized as an environmental hazard with the potential for inducing chemical and physiological disturbances of the endocrine, cardiovascular and nervous systems, in addition to its effects on audition (Leake 1970). Several investigators have reported a relationship between noise exposure and elevated peripheral resistance and thus blood pressure in humans (Jonsson & Hansson 1977; Andren et al. 1979). Investigations with rats have also indicated that noise exposure may contribute to elevated blood
pressure (Medoff & Bongiovanni 1945; Yeakel et al. 1948; Borg 1978a, b, c). Since it is known that noise exposure of a short duration significantly alters blood pressure, heart rate and peripheral vascular tone, the cardiovascular system has been chosen as a model. Recently, many reports reveal that the vascular endothelium plays an important role in many cardiovascular diseases, such as hypertension, stroke and atherosclerosis (Konishi & Su 1983; Lockette et al. 1986; Bossaier et a/. 1987;
Correspondence: Chin-Chen Wu, Department of Pharmacology, National Defense Medical Center, Taipei P.O. Box 90048-504, Taiwan.
834
C-C. Wu et al.
Rosenblum et al. 1987; Yamamoto et al. 1988; Rosenblum et al. 1989). The mechanism(s) by which noise exposure may lead to elevations in blood pressure and the effect of noise exposure on vascular reactivity have not been fully elucidated. One possibility is that noise may alter the function of the vascular endothelium, which may in turn elevate blood pressure by increasing vascular resistance. This hypothesis was evaluated by investigating the effects of noise on in virro vascular reactivities and by exploring the possible role of the endothelium in the relationship between noise and elevations in blood pressure.
METHODS Male Sprague-Dawley rats (220-250 g) were exposed to noise in Plexiglas cylindrical cages. The rats had sufficient room to move freely inside the cages. A loudspeaker (Speaderlab, WA, USA; Model KR4580) was mounted 30 cm above the cage and activated by a white noise generator (Lehigh Valley Electronics, USA; Model 581-02) powered by an amplifier system (HewlettPackard, CA, USA; 467A power amplifier and 6215A power supply). The frequency range of the noise generated was up to 1 kHz. Noise intensity was measured with a sound meter (B&K Inc, IL, USA.) and found to be uniform inside the cage. In each experiment, rats were exposed to white noise at 100 dB for 4 h per day, 6 days per week for 2 or 4 weeks. Control animals were sham-exposed (i.e. they were placed in the exposure cage and exposed to the ambient noise for the same exposure cage from 8:30 h to 12:30 h. At the end of the exposure period, rats were returned to the home cage and sacrificed 24 h later. Blood pressures were measured by the tail-cuff method and taken before rats were exposed to the noise and at 2 week intervals. The measurement of blood pressure was made at around 8:OO h. Before rats were sacrificed, they were anaesthetized with urethane (1.2 g/ kg, i.p.) and thoracic aortas were cut from control and noise-treated rats. These preparations were immediately placed in a cold physiological salt solution (PSS) of the following composition (mmol/ L): NaCl 118, KCI 4.7, NaHCO3 25, KH2P04 1.2, MgC12 1.25, CaCl2 2.5 and glucose 11. The connective tissue around the blood vessels was removed. Each segment of the vessels was cut into rings about 4 mm in length. Care was taken to preserve the endothelium of the vascular rings. The rings were suspended in a tissue bath containing 20 mL PSS (37°C) bubbled with a mixture of 95% 0 2 and 5% COz, and connected to Grass FT03C force transducers. The changes of vascular tension were recorded iso-
metrically on a Grass Model 7D polygraph. All preparations were equilibrated for 60-90 min under a resting tension of 3.0 g, which was the optimal tension for the aortic rings of both rats. After the equilibration period, a submaximal vasoconstriction was elicited with phenylephrine (0.3 pmol/ L) on the aortic rings. Then, acetylcholine (ACh; 1.0 pmol/ L) was added for 5 min to determine whether the endothelium had been mechanically injured. This procedure was repeated once in each preparation. Drugs were then removed from the bath by several washes with PSS and the rings were allowed to relax to study vascular reactivities in a cumulative manner. In relaxation studies, the rings were precontracted with phenylephrine (0.3 pmol/ L). After the contraction had reached a steady state, the vasodilators were added to the tissue bath in a cumulative manner. The vessels were then incubated for 10min with Nu-nitro+ arginine (50 pmol/L; Ishii et al. 1990) or methylene blue (10 pmol/L; Martin et al. 1985), and the experiment of ACh-induced relaxations was repeated. If the inhibitors by themselves induced an increase in tension or potentiated the contraction evoked by phenylephrine, the added concentration of phenylephnne was adjusted to match the level of contraction reached in the corresponding control experiment.
Chemicals Drugs used in this study were phenylephrine HC1 (Sigma Chemical Co., St. Louis, MO, USA), 5hydroxytryptamine (serotonin) creatinine sulfate (Sigma), acetylcholine chloride (Sigma), calcium ionophore A23 187 (Sigma), nitroglycerin (American Critical Care, American Hospital Supply Co., McGaw Park, IL, USA), NW-nitro-L-arginine methylester (Sigma) and methylene blue (Sigma). All concentrations are expressed as final molar concentrations in the tissue bath.
Statistical analysis
*
Data are reported as mean s.e.m. Statistical evaluation was performed using multiple comparison (Dunnett) following one-way analysis of variance (ANOVA). A value of P
