Artificial light at night affects the daily profile of pulse pressure and protein expression in the thoracic aorta of rats.

Artificial light at night (ALAN) disrupts 24-h variability of blood pressure, but the molecular mechanisms underlying these effects are unknown. Therefore, we analysed the daily variability of pulse pressure, the maximum value of acceleration rate of aortic pressure (dP/dt(max)) measured by telemetry and protein expression in the thoracic aorta of normotensive male rats exposed to ALAN (1-2 lx) for 3 weeks. Daily, 24-h variability of pulse pressure and dP/dt(max) was observed during a regular light/dark regimen with higher values during the dark compared to the light phase of the day. ALAN suppressed 24-h variability and enhanced ultradian (<12-h) periods of pulse pressure and dP/dt(max) in duration-dependent manners. From beat-to-beat blood pressure variability, ALAN decreased low-frequency bands (a sympathetic marker) and had minimal effects on high-frequency bands. At the molecular level, ALAN decreased angiotensin II receptor type 1 expression and reduced 24-h variability. ALAN caused the appearance of 12-h oscillations in transforming growth factor ß1 and fibulin 4. Expression of sarco/endoplasmic reticulum Ca2+-ATPase type 2 was increased in the middle of the light and dark phase of the day, and ALAN did not affect its daily and 12-h variability. In conclusion, ALAN suppressed 24-h variability of pulse pressure and dP/dt(max), decreased the power of low-frequency bands and differentially affected the expression of specific proteins in the rat thoracic aorta. Suppressed 24-h oscillations by ALAN underline the pulsatility of individual endocrine axes with different periods, disrupting the cardiovascular control of central blood pressure.

Artificial light at night suppresses the day-night cardiovascular variability: evidence from humans and rats.

Artificial light at night (ALAN) affects most of the population. Through the retinohypothalamic tract, ALAN modulates the activity of the central circadian oscillator and, consequently, various physiological systems, including the cardiovascular one. We summarised the current knowledge about the effects of ALAN on the cardiovascular system in diurnal and nocturnal animals. Based on published data, ALAN reduces the day-night variability of the blood pressure and heart rate in diurnal and nocturnal animals by increasing the nocturnal values of cardiovascular variables in diurnal animals and decreasing them in nocturnal animals. The effects of ALAN on the cardiovascular system are mainly transmitted through the autonomic nervous system. ALAN is also considered a stress-inducing factor, as glucocorticoid and glucose level changes indicate. Moreover, in nocturnal rats, ALAN increases the pressure response to load. In addition, ALAN induces molecular changes in the heart and blood vessels. Changes in the cardiovascular system significantly depend on the duration of ALAN exposure. To some extent, alterations in physical activity can explain the changes observed in the cardiovascular system after ALAN exposure. Although ALAN acts differently on nocturnal and diurnal animals, we can conclude that both exhibit a weakened circadian coordination among physiological systems, which increases the risk of future cardiovascular complications and reduces the ability to anticipate stress.

Mineralocorticoid receptor blockade protects the kidneys but does not affect inverted blood pressure rhythm in hypertensive transgenic (mRen-2)27 rats.

Aldosterone regulates blood pressure (BP) through water and sodium balance. In our study, we studied if continuous treatment with a mineralocorticoid receptor antagonist, spironolactone (30 mg/kg/day) for 20 days can: 1) attenuate hypertension development and restore inverted 24-h BP rhythm in hypertensive transgenic (mRen-2)27 rats (TGR) measured by telemetry; 2) improve function of the kidneys and heart; 3) be protective against high salt load (1% in water) by mitigating oxidative injury and improving kidney function. Spironolactone decreased albuminuria and 8-isoprostane in normal and salt load conditions in BP-independent effects. Salt load increased BP, impaired autonomic balance, suppressed plasma aldosterone level and increased natriuresis, albuminuria and oxidative injury in TGR. Spironolactone did not restore the inverted 24-h rhythm of BP in TGR, therefore, mineralocorticoids are not crucial in regulation of BP daily profile. Spironolactone improved kidney function, decreased oxidative stress and was protective against high salt load in the BP-independent manner.

Hypotensive effects of melatonin in rats: Focus on the model, measurement, application, and main mechanisms.

The hypotensive effects of melatonin are based on a negative correlation between melatonin levels and blood pressure in humans. However, there is a positive correlation in nocturnal animals that are often used as experimental models in cardiovascular research, and the hypotensive effects and mechanism of melatonin action are often investigated in rats and mice. In rats, the hypotensive effects of melatonin have been studied in normotensive and spontaneously or experimentally induced hypertensive strains. In experimental animals, blood pressure is often measured indirectly during the light (passive) phase of the day by tail-cuff plethysmography, which has limitations regarding data quality and animal well-being compared to telemetry. Melatonin is administered to rats in drinking water, subcutaneously, intraperitoneally, or microinjected into specific brain areas at different times. Experimental data show that the hypotensive effects of melatonin depend on the experimental animal model, blood pressure measurement technique, and the route, time and duration of melatonin administration. The hypotensive effects of melatonin may be mediated through specific membrane G-coupled receptors located in the heart and arteries. Due to melatonin's lipophilic nature, its potential hypotensive effects can interfere with various regulatory mechanisms, such as nitric oxide and reactive oxygen species production and activation of the autonomic nervous and circadian systems. Based on the research conducted on rats, the cardiovascular effects of melatonin are modulatory, delayed, and indirect.

Prenatal Hypoxia Affects Foetal Cardiovascular Regulatory Mechanisms in a Sex- and Circadian-Dependent Manner: A Review.

Prenatal hypoxia during the prenatal period can interfere with the developmental trajectory and lead to developing hypertension in adulthood. Prenatal hypoxia is often associated with intrauterine growth restriction that interferes with metabolism and can lead to multilevel changes. Therefore, we analysed the effects of prenatal hypoxia predominantly not associated with intrauterine growth restriction using publications up to September 2021. We focused on: (1) The response of cardiovascular regulatory mechanisms, such as the chemoreflex, adenosine, nitric oxide, and angiotensin II on prenatal hypoxia. (2) The role of the placenta in causing and attenuating the effects of hypoxia. (3) Environmental conditions and the mother's health contribution to the development of prenatal hypoxia. (4) The sex-dependent effects of prenatal hypoxia on cardiovascular regulatory mechanisms and the connection between hypoxia-inducible factors and circadian variability. We identified that the possible relationship between the effects of prenatal hypoxia on the cardiovascular regulatory mechanism may vary depending on circadian variability and phase of the days. In summary, even short-term prenatal hypoxia significantly affects cardiovascular regulatory mechanisms and programs hypertension in adulthood, while prenatal programming effects are not only dependent on the critical period, and sensitivity can change within circadian oscillations.

Artificial light at night suppresses the expression of sarco/endoplasmic reticulum Ca2+ -ATPase in the left ventricle of the heart in normotensive and hypertensive rats.

NEW FINDINGS: What is the central question of this study? Artificial light at night decreases blood pressure and heart rate in rats. Are these changes in heart rate accompanied by changes in protein expression in the heart's left ventricle? What is the main finding and its importance? Five weeks of artificial light at night affected protein expression in the heart's left ventricle in normotensive and hypertensive rats. Artificial light at night decreased expression of the sarco/endoplasmic reticulum Ca2+ -ATPase, angiotensin II receptor type 1 and endothelin-1. ABSTRACT: Artificial light at night (ALAN) affects the circadian rhythm of the heart rate in normotensive Wistar rats (WT) and spontaneously hypertensive rats (SHR) through the autonomic nervous system, which regulates the heart's activity through calcium handling, an important regulator in heart contractility. We analysed the expression of the sarco/endoplasmic reticulum Ca2+ -ATPase (SERCA2) and other selected regulatory proteins involved in the regulation of heart contractility, angiotensin II receptor type 1 (AT1 R), endothelin-1 (ET-1) and tyrosine hydroxylase (TH), in the left ventricle of the heart in WT and SHR after 2 and 5 weeks of ALAN with intensity 1-2 lx. Expression of SERCA2 was decreased in WT (control: 0.53 ± 0.07; ALAN: 0.46 ± 0.10) and SHR (control: 0.72 ± 0.18; ALAN: 0.56 ± 0.21) after 5 weeks of ALAN (P = 0.067). Expression of AT1 R was significantly decreased in WT (control: 0.51 ± 0.27; ALAN: 0.34 ± 0.20) and SHR (control: 0.38 ± 0.07; ALAN: 0.23 ± 0.09) after 2 weeks of ALAN (P = 0.028) and in SHR after 5 weeks of ALAN. Expression of ET-1 was decreased in WT (control: 0.51 ± 0.27; ALAN: 0.28 ± 0.12) and SHR (control: 0.54 ± 0.10; ALAN: 0.35 ± 0.23) after 5 weeks of ALAN (P = 0.015). ALAN did not affect the expression of TH in WT or SHR. In conclusion, ALAN suppressed the expression of SERCA2, AT1 R and ET-1, which are important for the regulation of heart contractility, in a strain-dependent pattern in both WT and SHR.

Prenatal hypoxia increases blood pressure in male rat offspring and affects their response to artificial light at night.

Prenatal hypoxia (PH) has negative consequences on the cardiovascular system in adulthood and can affect the responses to additional insults later in life. We explored the effects of PH imposed during embryonic day 20 (10.5% O2 for 12 h) on circadian rhythms of systolic blood pressure (BP) and heart rate (HR) in mature male rat offspring measured by telemetry. We evaluated: (1) stability of BP and HR changes after PH; (2) circadian variability of BP and HR after 2 and 5 weeks of exposure to artificial light at night (ALAN; 1-2 lx); and (3) response of BP and HR to norepinephrine. PH increased BP in the dark (134 ± 2 mmHg vs. control 127 ± 2 mmHg; p = 0.05) and marginally in the light (125 ± 1 mmHg vs. control 120 ± 2 mmHg) phase of the day but not HR. The effect of PH was highly repeatable between 21- and 27-week-old PH male offspring. Two weeks of ALAN decreased the circadian variability of HR (p < 0.05) and BP more in control than PH rats. After 5 weeks of ALAN, the circadian variability of HR and BP were damped compared to LD and did not differ between control and PH rats (p < 0.05). Responses of BP and HR to norepinephrine did not differ between control and PH rats. Hypoxia at the end of the embryonic period increases BP and affects the functioning of the cardiovascular system in mature male offspring. ALAN in adulthood decreased the circadian variability of cardiovascular parameters, more in control than PH rats.

Dim light at night attenuates circadian rhythms in the cardiovascular system and suppresses melatonin in rats.

AIMS: Cardiovascular parameters exhibit significant 24-h variability, which is coordinated by the suprachiasmatic nucleus (SCN), and light/dark cycles control SCN activity. We aimed to study the effects of light at night (ALAN; 1-2 lx) on cardiovascular system control in normotensive rats. MAIN METHODS: Heart rate (HR) and blood pressure (BP) were measured by telemetry during five weeks of ALAN exposure. From beat-to-beat telemetry data, we evaluated spontaneous baroreflex sensitivity (sBRS). After 2 (A2) and 5 (A5) weeks of ALAN, plasma melatonin concentrations and the response of BP and HR to norepinephrine administration were measured. The expression of endothelial nitric oxide synthase (eNOS) and endothelin-1 was determined in the aorta. Spontaneous exploratory behaviour was evaluated in an open-field test. KEY FINDINGS: ALAN significantly suppressed the 24-h variability in the HR, BP, and sBRS after A2, although the parameters were partially restored after A5. The daily variability in the BP response to norepinephrine was reduced after A2 and restored after A5. ALAN increased the BP response to norepinephrine compared to the control after A5. Increased eNOS expression was found in arteries after A2 but not A5. Endothelin-1 expression was not affected by ALAN. Plasma melatonin levels were suppressed after A2 and A5. Spontaneous exploratory behaviour was reduced. SIGNIFICANCE: ALAN decreased plasma melatonin and the 24-h variability in the haemodynamic parameters and increased the BP response to norepinephrine. A low intensity ALAN can suppress circadian control of the cardiovascular system with negative consequences on the anticipation of a load.

Consequences of low-intensity light at night on cardiovascular and metabolic parameters in spontaneously hypertensive rats 1.

Circadian rhythms are an inherent property of physiological processes and can be disturbed by irregular environmental cycles, including artificial light at night (ALAN). Circadian disruption may contribute to many pathologies, such as hypertension, obesity, and type 2 diabetes, but the underlying mechanisms are not understood. Our study investigated the consequences of ALAN on cardiovascular and metabolic parameters in spontaneously hypertensive rats, which represent an animal model of essential hypertension and insulin resistance. Adult males were exposed to a 12 h light - 12 h dark cycle and the ALAN group experienced dim light at night (1-2 lx), either for 2 or 5 weeks. Rats on ALAN showed a loss of light-dark variability for systolic blood pressure, but not for heart rate. Moreover, a gradual increase of systolic blood pressure was recorded over 5 weeks of ALAN. Exposure to ALAN increased plasma insulin and hepatic triglyceride levels. An increased expression of metabolic transcription factors, Pparα and Pparγ, in the epididymal fat and a decreased expression of Glut4 in the heart was found in the ALAN group. Our results demonstrate that low-intensity ALAN can disturb blood pressure control and augment insulin resistance in spontaneously hypertensive rats, and may represent a serious risk factor for cardiometabolic diseases.

The exaggerated salt-sensitive response in hypertensive transgenic rats (TGR mRen-2) fostered by a normotensive female.

Suboptimal conditions during prenatal and early postnatal development can increase risk of hypertension later in life. We studied consequences of a changed perinatal environment by initiating the cross-fostering of homozygous Ren-2 transgenic rat (TGR) offspring to normotensive, transgene-negative control mothers, and vice versa. We hypothesized that cross-fostering to a normotensive female can attenuate the development of malignant hypertension in TGR offspring (TGRx) and change their salt-sensitive response. Blood pressure (BP) was monitored by the telemetry system under normal salt intake, and BP responses to increased salt intake in the phase of established hypertension. Under normal salt conditions, BP was not markedly different in cross-fostered animals compared with controls. However, BP responses to 2% salt intake led to a stronger BP response in TGRx during the active phase when compared with the control TGR group. The TGRx also exhibited increased albuminuria, lower sodium excretion, and creatinine clearance under higher salt intake compared with control salt intake. Higher salt intake resulted in a significant increase of aldosterone concentrations only in the TGRx group; moreover, TGRx rats exhibited more pronounced renal injury compared with controls. In conclusion, our data indicate that cross-fostering in TGR not only did not attenuate the development of hypertension but, on the contrary, led to the deterioration of BP regulation, particularly due to exaggerated salt sensitivity and sodium retention in TGRx. Results underline the important role of the mother during lactation in postnatal development of the offspring, since these changes reflected different ion content in milk of a particular strain of rats.