P-322: Alterations in blood pressure and heart rate during cyclic changes in food intake

In people trying to loose body weight, cycles of hypophagia followed by hyperphagia are quite common. The aim of the present study was to evaluate the alterations in daily mean arterial pressure (MAP) and heart rate (HR) during short-term (5-day) changes in food intake. Adult male lop-eared rabbits were instrumented for continuous measurement of blood pressure and HR by telemetry (24 hours/day) and fed 150 g/day of maintenance diet. The animals were subjected to five 14-day periods. Each period consisted of 5 days where food intake (normal chow) was randomly set to either 225 g (+50 %), 187 g (+25 %), 112 g (-25 %), 75 g (-50 %) per day or ad libitum, followed by 9 days of recovery at 150 g/day. A 50 % increase in food intake induced an immediate and significant increase in HR and a slight increase in MAP (+24.7 ± 2.8 bpm and +2.2 ± 0.6 mmHg at day 5). Similarly, a 50 % decrease in food intake induced a decrease in HR and MAP (-29.0 ± 1.8 bpm and -5.9 ± 1.3 mmHg at day 5). Food access ad libitum induced an even more pronounced increase in HR and MAP (+43.3 ± 3.9 bpm and +4.4 ± 0.8 mmHg at day 5). Unlike the increase in HR during hyperphagia which reached plateau after 1 day, the decrease in HR during hypophagia was progressive (-29.0 ± 1.8 on day 5 vs. -17.2 ± 2.1 bpm on day 1 of -50 %). The effect of hyperphagia on MAP and HR was reversible within 1 day, except after food ad libitum. Recovery of MAP and HR following hypophagia was rapid, but not complete. Our data suggest that short-term quantitative variations in food intake can lead to pronounced changes in daily hemodynamics, with different courses for hyper- vs. hypophagia. These alterations may play an important role in explaining the increased cardiovascular morbidity associated with weight cyclin

Serial changes in cardiovascular and renal function of rabbits ingesting a high-fat, high-calorie diet

To explore the mechanisms of obesity-induced hypertension we analyzed the sequential changes in cardiovascular and renal function in adult rabbits switched to high-fat diet (HFD) for 8 weeks. Animals were housed in metabolic cages for continuous 24-h recording of arterial pressure by telemetry and daily urine collection. High-fat diet induced a progressive increase in body weight (+47%) and a rapid rise in mean arterial pressure, heart rate, and glomerular filtration rate that stabilized, respectively, at 14%, 31% and 68% greater than control values. Time-course analysis of changes in blood pressure may reveal two components of obesity-induced hypertension, an early phase related to HFD itself and a later phase related to weight gain. Am J Hypertens 1999;12:826-829 © 1999 American Journal of Hypertension, Lt

Short-term (5-day) changes in food intake alter daily hemodynamics in rabbits

Background: In humans, particularly among individuals trying to lose weight, cycles of hypophagia followed by cycles of hyperphagia are quite common and may lead to an increased cardiovascular morbidity. The aim of the present study was to evaluate the alterations in daily mean arterial pressure (MAP) and heart rate (HR) during short-term (5-day) changes in food intake. Methods: Adult male rabbits instrumented for continuous (24 h/day) telemetric recording of blood pressure (BP) and HR were subjected to five 14-day periods of altered food intake. Each period consisted of 5 days in which food intake was set to −50%, −25%, +25%, +50%, or +100% (food ad libitum) per day followed by 9 days at 150 g/day of maintenance diet. Results: The increase in food intake induced an immediate and significant increase in HR and a less pronounced increase in MAP. Similarly, a 25% and 50% decrease in food intake induced a decrease in HR and MAP. Unlike the increase in HR during hyperphagia, which reached a plateau after 1 day, the decrease in HR during hypophagia was progressive. The effect of hyperphagia on MAP and HR was reversible within 1 day, whereas hypophagia induced changes were persistent over several days. Conclusions: A highly significant linear relationship can be established across the alterations in food intake (from −50% to +100%) and the respective changes in blood pressure (BP) or HR. These data suggest that prompt changes in hemodynamics induced by alterations in food intake might be implicated in the early events during weight gain or during weight loss. Am J Hypertens 2003;16:302-306 @ 2003 American Journal of Hypertension, Lt

Role of the sympathetic nervous system during the development of obesity-induced hypertension in rabbits

We have previously reported that weight gain induced by high-fat diet (HFD) leads to an increase in mean arterial pressure (MAP, +14%) and heart rate (HR, +31%) in the adult rabbit. In the present study, we tested the hypothesis that an increased activity of the sympathetic nervous system may contribute to the development of obesity-induced hypertension. A combination of α- and β-adrenergic blockers (terazosin + propranolol) was chronically administered to rabbits housed in metabolic cages for continuous monitoring of arterial pressure by telemetry, 24 h a day. After 2 weeks of adrenergic blockade under control diet, animals were switched to HFD for the next 6 weeks. HFD induced a progressive increase in body weight, but no increase in mean arterial pressure (+0.2 ± 2.5%) and a slight increase in heart rate (+14 ± 3%). Time-control animals fed normal diet showed no changes in MAP or HR with long-term α- and β-adrenergic blockade. Our results indicate that the activation of the sympathetic nervous system may play an important role in the pathogenesis of obesity-induced hypertensio

Hemodynamic consequences of chronic parasympathetic blockade with a peripheral muscarinic antagonist

hereas the sympathetic nervous system has a well-established role in blood pressure (BP) regulation, it is not clear whether long-term levels of BP are affected by parasympathetic function or dysfunction. We tested the hypothesis that chronic blockade of the parasympathetic nervous system has sustained effects on BP, heart rate (HR), and BP variability (BPV). Sprague-Dawley rats were instrumented for monitoring of BP 22-h per day by telemetry and housed in metabolic cages. After the rats healed from surgery and a baseline control period, scopolamine methyl bromide (SMB), a peripheral muscarinic antagonist, was infused intravenously for 12 days. This was followed by a 10-day recovery period. SMB induced a rapid increase in mean BP from 98 ± 2 mmHg to a peak value of 108 ± 2 mmHg on day 2 of the SMB infusion and then stabilized at a plateau value of +3 ± 1 mmHg above control (P < 0.05). After cessation of the infusion, the mean BP fell by 6 ± 1 mmHg. There was an immediate elevation in HR that remained significantly above control on the last day of SMB infusion. SMB also induced a decrease in short-term (within 30-min periods) HR variability and an increase in both short-term and long-term (between 30-min periods) BPV. The data suggest that chronic peripheral muscarinic blockade leads to modest, but sustained, increases in BP, HR, and BPV, which are known risk factors for cardiovascular morbidity

Role of mutation of the circadian clock gene Per2 in cardiovascular circadian rhythms

Alterations in the circadian blood pressure pattern are frequently observed in hypertension and lead to increased cardiovascular morbidity. However, there are no studies that have investigated a possible implication of the Period2 gene, a key component of the molecular circadian clock, on the circadian rhythms of blood pressure and heart rate. To address this question, we monitored blood pressure, heart rate and locomotor activity 24h a day by telemetry in mice carrying a mutation in the Period2 gene and in wild type control mice. Under a standard 12h/12h light-dark cycle mutant mice showed a mild cardiovascular phenotype with an elevated 24h heart rate, a decreased 24h diastolic blood pressure and an attenuation of the dark-light difference in blood pressure and heart rate. Locomotor activity was similar in both groups and did not appear to explain the observed hemodynamic differences. When mice were placed under constant darkness during 8 consecutive days, wild type mice maintained 24h rhythms whereas there was an apparent progressive loss of 24h rhythm of blood pressure, heart rate and locomotor activity in mutant mice. However, a chi-square periodogram revealed that circadian rhythms were preserved under complete absence of any light cue, but with shorter periods by about 40 min, leading to a cumulative phase shift towards earlier times of about 5h and 20 min by the end of the 8th day. When heart rate, mean arterial pressure and activity were recalculated according to the endogenous circadian periods of each individual mouse, the amplitudes of the circadian rhythms ("subjective night"-"subjective day" differences) were maintained for all variables studied. Our data show that mutation of the Period2 gene results in an attenuated dipping of blood pressure and heart rate during both light-dark cycles and constant darkness, and in shorter circadian periods during constant darkness

Ectopic fat storage in heart, blood vessels and kidneys in the pathogenesis of cardiovascular diseases

In humans and most animal models, the development of obesity leads not only to increased fat depots in classical adipose tissue locations but also to significant lipid deposits within and around other tissues and organs, a phenomenon known as ectopic fat storage. The purpose of this review is to explore the possible locations of ectopic fat in key target-organs of cardiovascular control (heart, blood vessels and kidneys) and to propose how ectopic fat storage can play a role in the pathogenesis of cardiovascular diseases associated with obesity. In animals fed a high-fat diet, cardiac fat depots within and around the heart impair both systolic and diastolic functions, and may in the long-term promote heart failure. Accumulation of fat around blood vessels (perivascular fat) may affect vascular function in a paracrine manner, as perivascular fat cells secrete vascular relaxing factors, proatherogenic cytokines and smooth muscle cell growth factors. Furthermore, high amounts of perivascular fat could mechanically contribute to the increased vascular stiffness seen in obesity. Finally, accumulation of fat in the renal sinus may limit the outflow of blood and lymph from the kidney, which would alter intrarenal physical forces and promote sodium reabsorption and arterial hypertension. Taken together, ectopic fat storage in key target-organs of cardiovascular control may impair their functions, contributing to the increased prevalence of cardiovascular diseases in obese subjects

Address for correspondence:

Montani et al., Ectopic fat storage in key cardiovascular organs 1 Ectopic fat storage in heart, blood vessels and kidneys in th