Cardiovascular effects of nonproteolytic activation of prorenin.
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Adaptor Proteins, Signal Transducing↗
Biomedical subjects
Dinko Susic
Publications and source records attributed to Dinko Susic.
Salt loading produces severe renal hemodynamic dysfunction independent of arterial pressure in spontaneously hypertensive rats.
We have previously shown that salt excess has adverse cardiac effects in spontaneously hypertensive rats (SHR), independent of its increased arterial pressure; however, the renal effects have not been reported. In the present study we evaluated the role of three levels of salt loading in SHR on renal function, systemic and renal hemodynamics, and glomerular dynamics. At 8 wk of age, rats were given a 4% (n = 11), 6% (n = 9), or 8% (n = 11) salt-load diet for the ensuing 8 wk; control rats (n = 11) received standard chow (0.6% NaCl). Rats had weekly 24-h proteinuria and albuminuria quantified. At the end of salt loading, all rats had systemic and renal hemodynamics measured; glomerular dynamics were specially studied by renal micropuncture in the control, 4% and 6% salt-loaded rats. Proteinuria and albuminuria progressively increased by the second week of salt loading in the 6% and 8% salt-loaded rats. Mean arterial pressure increased minimally, and glomerular filtration rate decreased in all salt-loaded rats. The 6% and 8% salt-loaded rats demonstrated decreased renal plasma flow and increased renal vascular resistance and serum creatinine concentration. Furthermore, 4% and 6% salt-loaded rats had diminished single-nephron plasma flow and increased afferent and efferent arteriolar resistances; glomerular hydrostatic pressure also increased in the 6% salt-loaded rats. In conclusion, dietary salt loading as low as 4% dramatically deteriorated renal function, renal hemodynamics, and glomerular dynamics in SHR independent of a minimal further increase in arterial pressure. These findings support the concept of a strong independent causal relationship between salt excess and cardiovascular and renal injury.
Albuminuria↗
Long-term mineralocorticoid receptor blockade reduces fibrosis and improves cardiac performance and coronary hemodynamics in elderly SHR.
Aldosterone has been implicated as one of the mediators of cardiovascular injury in various diseases. This study examines whether mineralocorticoid antagonism ameliorates or prevents the adverse cardiac effects of hypertension and aging. Male 22-wk-old spontaneously hypertensive rats (SHR) were divided into two groups, 15 rats in each. One group received no treatment; the other was given eplerenone ( approximately 100 mg.kg(-1).day(-1)). At the age of 54 wk, indexes of cardiovascular mass, systemic and regional hemodynamics, including coronary, left ventricular function, and myocardial collagen content, were determined in all rats. Hemodynamic studies were done in conscious rats. Arterial pressure was lowered only slightly in eplerenone-treated rats, and cardiac output and total peripheral resistance did not differ from control rats. Left and right ventricular and aortic mass indexes were unaffected by eplerenone; however, concentration of hydroxyproline in the right and left ventricle was decreased significantly (P < 0.05) by eplerenone. This was accompanied by an improvement in left ventricular diastolic function and coronary hemodynamics. In conclusion, long-term therapy with the mineralocorticoid receptor antagonist eplerenone ameliorated adverse cardiac effects of both hypertension and aging in SHR. Thus reduction in myocardial fibrosis, paralleled by improvements in left ventricular function and coronary hemodynamics, was observed in eplerenone-treated SHR.
Animals↗
Myocardial fibrosis, impaired coronary hemodynamics, and biventricular dysfunction in salt-loaded SHR.
Arterial pressure in most experimental and clinical hypertensions is exacerbated by salt. The effects of salt excess on right and left ventricular (RV and LV, respectively) functions and their respective coronary vasodilatory responses have been less explored. We therefore examined the effects of 8 wk of NaCl excess (8% in food) on arterial pressure, RV and LV functions (maximal rate of increase and decrease of ventricular pressure; dP/dt(max) and dP/dt(min)), coronary hemodynamics (microspheres), and collagen content (hydroxyproline assay and collagen volume fraction) in young adult normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR), aged 16 wk by the end of the study. Prolonged salt excess in WKY and SHR elevated pressure only modestly, but it markedly increased LV mass, especially in SHR. Moreover, salt excess significantly impaired RV and LV diastolic function in SHR but only LV diastolic function in WKY rats. However, salt loading affected neither RV nor LV contractile function in both strains. Interstitial and perivascular collagen deposition was increased, whereas coronary vasodilatory responses to dipyridamole diminished in both ventricles in the salt-loaded SHR but not in WKY rats. Therefore, accumulation of ventricular collagen as well as altered myocardial perfusion importantly contributed to the development of salt-related RV and LV dysfunctions in this model of naturally occurring hypertension. The unique effects of salt loading on both ventricles in SHR, but not WKY rats, strongly suggest that nonhemodynamic mechanisms in hypertensive disease participate pathophysiologically with salt-loading hypertension. These findings point to the conclusion that the concept of "salt sensitivity" in hypertension is far more complex than simply its effects on arterial pressure or the LV.
Animals↗
Validation of echocardiographic and Doppler indexes of left ventricular relaxation in adult hypertensive and normotensive rats.
This study was performed to validate echocardiographic and Doppler techniques for the assessment of left ventricular (LV) diastolic function in spontaneously hypertensive rats (SHR) and normotensive Wistar rats. In 11 Wistar rats and 20 SHR, we compared 51 sets of invasive and Doppler LV diastolic indexes. Noninvasive indexes of LV relaxation were related to the minimal rate of pressure decline (-dP/dt(min)), particularly isovolumic relaxation time (IVRT), the Tei index, the early velocity of the mitral annulus (E(m)) using Doppler tissue imaging, and early mitral flow propagation velocity using M-mode color (r = 0.28-0.56 and P < 0.05-0.0001). When the role of systolic load was considered, the correlation between Doppler indexes of LV diastolic function and relaxation rate [(-dP/dt(min))/LV systolic pressure] improved (r = 0.48-0.86 and P = 0.004-0.0001, respectively). Similarly, Doppler indexes of LV diastolic function and the time constant of isovolumic LV relaxation (tau) correlated well (r = 0.50-0.84 and P = 0.0002-0.0001, respectively). In addition, eight SHR and eight Wistar rats were compared; their LV end-diastolic diameters were similar, whereas the SHR LV mass was greater. Furthermore, IVRT and Tei index were significantly higher and E(m) was lower in SHR. Moreover, tau was higher in SHR, demonstrating impaired LV relaxation. In conclusion, LV relaxation can be assessed reliably using echocardiographic and Doppler techniques, and, using these indexes, impaired relaxation was demonstrated in SHR.
Animals↗
Beneficial cardiovascular actions of eplerenone in the spontaneously hypertensive rat.
BACKGROUND: Aldosterone has been implicated as a potential mediator of cardiac and vascular damage in a variety of disorders. This study examined the role of aldosterone and its interplay with the renin-angiotensin system in the pathogenesis of hypertension. To this end, the effects of the aldosterone antagonist eplerenone and the angiotensin converting enzyme inhibitor lisinopril on cardiovascular mass, myocardial collagen, and coronary circulation were examined in spontaneously hypertensive rats. METHODS: Male, 22-week-old rats were randomly divided into 4 groups (12 in each). The control group received no treatment, the second group was given eplerenone (100 mg/kg/day), the third received lisinopril (3 mg/kg/day), and the fourth was given eplerenone and lisinopril. After 12 weeks of respective treatments, systemic and regional hemodynamics and cardiovascular mass indexes were measured in conscious instrumented rats. RESULTS: Eplerenone decreased arterial pressure but did not affect left ventricular mass or hydroxyproline concentration (an estimate of collagen). It did, however, reduce minimal coronary vascular resistance and increased coronary flow reserve. Lisinopril decreased arterial pressure and ventricular mass but did not affect regional hemodynamics. The combination therapy produced synergistic effects. CONCLUSION: Aldosterone antagonism improved coronary and systemic hemodynamics in adult spontaneously hypertensive rats but did not affect cardiovascular mass indexes. The finding that lisinopril and eplerenone decreased arterial pressure to the same extent but had different cardiovascular effects suggested that these effects might be pressure independent.
Animals↗
Cardiac structural and functional responses to salt loading in SHR.
Increased dietary salt intake induces cardiac fibrosis in the spontaneously hypertensive rat (SHR), yet little information details its effects on left ventricular (LV) function. Additionally, young normotensive rats are more sensitive to the trophic effect of dietary sodium than older rats. Thus cardiac responses to salt loading were evaluated at two ages in the SHR; LV collagen content was also examined. SHR (8 or 20 wk of age) were given an 8% salt diet; their age-matched controls received standard chow. Echocardiographic indexes, arterial pressure, and LV hydroxyproline concentration were measured at 16 and 52 wk in the younger and older SHR groups, respectively. In most SHR, salt excess increased arterial pressure, LV mass, and hydroxyproline concentration and impaired LV relaxation manifested by prolonged isovolumic relaxation time, decreased early and atrial filling velocity ratio (V(E)/V(A)), and slower propagation velocity of E wave (V(P)). LV systolic function remained normal. However, one-quarter of the young salt-loaded SHR developed cardiac failure with systolic and diastolic dysfunction associated with greater LV mass and ventricular fibrosis. They also had lower arterial pressure, decreased fractional shortening, and a restrictive pattern of mitral flow. Moreover, the shorter deceleration time of the E wave and increased V(E)/V(P), an index of LV filling pressure, indicated increased LV stiffness in these rats. These findings demonstrated that sodium sensitivity in SHR is manifested not only by further pressure elevation but also by significant LV functional impairment that most likely is related to enhanced ventricular fibrosis. Moreover, the SHR are more susceptible to cardiac damage when high dietary salt is introduced earlier in life.
Aging↗
Monitoring of respiratory variations of aortic blood flow velocity using esophageal Doppler.
OBJECTIVE: The purpose of this study was to determine whether monitoring of respiratory changes in aortic blood flow velocity, recorded by esophageal Doppler, could be used to detect changes in volume depletion. DESIGN: Animal study. ANIMALS AND INTERVENTIONS: After general anesthesia and tracheotomy, ten New Zealand female rabbits, weighing 4-4.5 kg were studied under mechanical ventilation at a fixed tidal volume; during this time 5-ml blood samples were withdrawn (in increments up to a total of 30 ml) and then retransfused. MEASUREMENTS AND RESULTS: At each step, systolic (SBP), diastolic (DBP), pulse (PP) pressures and maximum descending aortic blood flow (V) were recorded. Respiratory changes of V (DeltaV), SBP (DeltaSBP) and PP (DeltaPP) were calculated as the difference of maximal and minimal values divided by their respective means and expressed as a percentage. The amount of blood withdrawn correlated negatively with SBP, DBP, PP and V and positively with DeltaSBP, DeltaPP and DeltaV. Among these parameters, DeltaV correlated best with the amount of blood withdrawn ( r=0.89, p<0.001) and it was the most accurate index of volume depletion. CONCLUSION: Monitoring of the respiratory variation in V, calculated by esophageal Doppler technique, seems to be a highly accurate index of blood volume depletion and restitution.
Analysis of Variance↗
Cardiovascular and renal effects of a collagen cross-link breaker (ALT 711) in adult and aged spontaneously hypertensive rats.
BACKGROUND: Increased formation of advanced glycosylation end-products on body proteins is a consequence of aging and leads to exaggerated collagen cross-linking eventually increasing cardiovascular stiffness. This study reports our initial inquires into the cardiovascular and renal effects of a cross-link breaker (ALT-711) in aged spontaneously hypertensive rats (SHR). METHODS AND RESULTS: The first experiment, in 45-week-old SHR, showed that (among four doses) the dose of 1 mg/kg/d of ALT-711 given for 4 months was most effective in reducing left ventricular and aortic mass indexes. ALT-711 also reduced left ventricular hydroxyproline concentration (5.8 +/- 0.2 v 5.1 +/- 0.3 mg/g in controls, P < .05); however, it did not affect systemic or regional hemodynamics. In older SHR, ALT-711 (1 mg/kg/d) reduced (P < .05) systolic pressure (tail-cuff) (from 203 +/- 3 mm Hg at outset to 187 +/- 3 mm Hg at 8 weeks). Systolic pressure remained unchanged in placebo-treated rats. In addition, left ventricular index (3.09 +/- 0.10 v 3.44 +/- 0.05 mg/g) and aortic mass index (1.54 +/- 0.04 v 1.74 +/- 0.05 mg/mm) were reduced by ALT-711. In the third experiment, 1-year-old SHR were given vehicle or ALT-711 (1 mg/kg/d) or placebo until natural death. After 3 months, ALT-711 markedly reduced urinary protein excretion (74.5 +/- 8.6 v 135.4 +/- 11.8 mg/24 h). Echocardiographic studies, performed at the outset and after 3 and 6 months, revealed two changed indexes. Left ventricular end-diastolic diameter increased more in control than in ALT rats, whereas E-wave deceleration time decreased more in control than in ALT rats. CONCLUSIONS: Therapy with ALT-711 exerted beneficial cardiovascular and renal effects in aged SHR, improving systolic pressure, left ventricular mass, geometry, and hydroxyproline content while reducing urinary protein excretion.
Animals↗
Crosslink breakers: a new approach to cardiovascular therapy.
PURPOSE OF REVIEW: Advanced glycation end-products accumulate on body proteins with aging, and their formation is greatly enhanced with rising plasma glucose level. Advanced glycation end-products bond together and, consequently, increase protein crosslinking. In the circulatory system, increased collagen crosslinking caused by advanced glycation end-products increases cardiovascular stiffness as well as the risk for cardiovascular morbidity and mortality. A breaker of advanced glycation end-products-related crosslinks, ALT-711, has been recently discovered. This review summarizes the latest evidence that breaking collagen crosslinks may be an efficient new therapeutic approach to the adverse cardiovascular and renal consequences of aging and diabetes. RECENT FINDINGS: The results of recent studies clearly demonstrated that ALT-711, a breaker of advanced glycation end-products-related protein crosslinks, ameliorated the adverse cardiovascular and renal changes associated with aging, diabetes, and hypertension. In diabetic animals, ALT-711 improved left ventricular function, decreased ventricular collagen content and improved its solubility, reduced aortic stiffness, ameliorated diabetic nephrosclerosis, and improved renal function. In older spontaneously hypertensive rats, it reduced left ventricular mass and collagen content, reduced proteinuria, and extended survival. The results of recent studies also indicated that the effects of crosslinks breakers may be mediated in part via reduction in oxidative stress and profibrotic cytokines. SUMMARY: The results of experimental studies and one clinical trial have clearly established the usefulness of ALT-711 in the therapy of the cardiovascular and renal disorders associated with aging, diabetes, and hypertension. Thus, breaking advanced glycation end-products-related collagen crosslinks has emerged as a new approach to cardiovascular therapy.
Aging↗
Collagen cross-link breakers: a beginning of a new era in the treatment of cardiovascular changes associated with aging, diabetes, and hypertension.
Aging, diabetes, and hypertension are conditions in which arterial and myocardial stiffness is increased. Increased arterial stiffness is manifested by an increased systolic arterial pressure, pulse pressure and pulse wave velocity, whereas increased myocardial stiffness is manifested by impaired left ventricular diastolic filling. Moreover, increased arterial stiffness increases cardiac workload, further aggravating already existing adverse changes in left ventricular structure and function. Indeed, studies in human beings have clearly shown that increased cardiovascular stiffness is a reliable predictor of cardiovascular morbidity and mortality. Increased cardiovascular stiffness is usually attributed to the development of fibrosis (i.e., accumulation of collagen). It has also been recognized that the increased cardiac and vascular stiffness may be due to increased collagen cross-linking due to the formation of advanced glycosylation end-products (AGEs). In agreement with this notion is the finding that an inhibitor of AGEs formation improves vascular stiffness in diabetic rats. More recently, cross-link breakers have been developed, and the beneficial effects of one such agent (ALT-711) have been shown in experimental and clinical settings. This report briefly summarizes age related changes in cardiovascular structure and function and describes results of experimental and clinical studies involving collagen cross-link breakers.
Aging↗
Beneficial pleiotropic vascular effects of rosuvastatin in two hypertensive models.
OBJECTIVES: The goal of this research was to study the effects of rosuvastatin on systemic and regional hemodynamics in two hypertensive rat models, one genetic, the other induced with inhibition of nitric oxide synthesis. BACKGROUND: Rats naturally have low cholesterol levels that are generally unaffected by statin therapy, thus providing a good model for studying cardiovascular effects unrelated to lipid metabolism. METHODS: Male 20-week-old spontaneously hypertensive rats (SHR) were divided into five groups and given either vehicle or 1, 5, 10, and 20 mg/kg of rosuvastatin daily, by gavage, for 12 weeks. Wistar-Kyoto rats (WKY) were divided into four groups; the first received vehicle and the second rosuvastatin (20 mg/kg). The third and fourth groups were given N(omega)-nitro-L-arginine (L-NAME) (15 mg/kg/day) in drinking water, and the fourth group received rosuvastatin daily, 20 mg/kg for six weeks. At the end of the respective treatments, systemic and organ hemodynamics (radionuclide-labeled microspheres) and cardiovascular mass were determined in all rats. RESULTS: Rosuvastatin reduced arterial pressure in SHR rats, but not in WKY/L-NAME rats. Total peripheral resistance decreased with rosuvastatin in both hypertensive models, whereas cardiac output increased with rosuvastatin in WKY/L-NAME rats. Neither cardiac nor aortic mass was changed. Regional hemodynamics improved with rosuvastatin in both hypertensive models, as evidenced by increased blood flows and decreased vascular resistances. No effect on plasma lipids was observed. CONCLUSIONS: These results showed that rosuvastatin reduced arterial pressure in genetic hypertension and improved systemic and regional hemodynamics in both hypertensive models independently of cholesterol levels. Thus rosuvastatin improved systemic and regional hemodynamics by reducing vascular resistance.
Animals↗
Long-term left ventricular echocardiographic follow-up of SHR and WKY rats: effects of hypertension and age.
Long-term follow-up of left ventricular (LV) function using echocardiography has not been reported and, in this study, was carried out in normotensive (WKY) rats and spontaneously hypertensive rats (SHR). In 10 WKY rats and SHR, LV diastolic and systolic diameter (LVEDD and LVSD), shortening fraction (SF), and weight (LVW) were determined at 8, 15, 20, 35, and 80 wk of age. The ratio of early to late mitral flow and mitral annulus velocity (VE/VA and Em/Am), isovolumic relaxation time (IVRT), deceleration time of the E wave (DTE), Tei index, and mitral flow propagation velocity (Vp) were measured. No difference in LVEDD was found between SHR and WKY rats; however, LVEDD was increased at 80 wk in both strains. SF decreased slightly in old WKY rats. LVW progressively increased from 20 to 80 wk in both strains and was greater in SHR. VE/VA and Em/Am decreased at 80 wk in WKY rats. LV relaxation (IVRT, Tei index, and Vp) was progressively impaired in SHR compared with WKY rats. LV compliance (DTE) was altered in old SHR. Echocardiography permitted a long follow-up of LV function in SHR and WKY rats. Ventricular relaxation was impaired early in the life of SHR and progressed with aging. Furthermore, LV compliance was altered, but systolic function remained unchanged, in old SHR. In contrast, relaxation and SF were only slightly altered in old WKY rats, suggesting that pressure-related changes in LV function were the dominant features in the SHR.
Aging↗
Omapatrilat induces profound renal vasodilation but does not affect coronary hemodynamics.
BACKGROUND: Omapatrilat has potent enzymatic inhibitory effects on the angiotensin-converting enzyme and neutral endopeptidase. The prolonged effects of this inhibition on systemic and regional hemodynamics, cardiovascular mass, and hydroxyproline concentration in spontaneously hypertensive rats were studied. The contribution of endogenous bradykinin on the cardiovascular actions of omapatrilat in this genetic model of hypertension was also investigated. METHODS AND RESULTS: Systemic and regional hemodynamics (radionuclide-labeled microspheres), left and right ventricular and aortic masses, and hydroxyproline concentration were determined in 35-week-old spontaneously hypertensive rats after 12 weeks of treatment with omapatrilat (40 mg/kg/day), with and without the bradykinin receptor antagonist icatibant (500 microg/kg/day). Omapatrilat decreased mean arterial pressure, reducing total peripheral resistance as well as decreased left ventricular and aortic mass indices. It also induced a profound renovasodilation associated with a decrease renal vascular resistance that markedly increased renal blood flow. Coronary hemodynamics and left ventricular hydroxyproline concentration remained unaltered. Concomitant blockade of bradykinin receptors partially attenuated the hypotensive effect of omapatrilat and its effect on aortic mass; and icatibant did not influence the renovasodilation. CONCLUSION: Omapatrilat produced profoundly beneficial effects on systemic and renal hemodynamics, as well as on left ventricular and aortic masses, without any effect on coronary hemodynamics. These effects of omapatrilat on arterial pressure and aortic mass, but not on renal hemodynamics and left ventricular mass, may have been at least partially mediated through the action of bradykinin.
Angiotensin-Converting Enzyme Inhibitors↗
Echocardiographic measurement of cardiac output in rats.
The systematic evaluation of different transthoracic echocardiographic (TTE) methods to determine cardiac output (CO) and the effect of changes in intravascular volume on echocardiographically determined indexes of cardiovascular structure in the rat has not been documented. With the use of 11 Wistar rats, simultaneous echocardiographic and thermodilution measurements of CO were compared at baseline and after blood withdrawal or transfusion at 43 different levels of intravascular volume and using 10 different echocardiographic approaches. The best correlation (r = 0.93; P < 0.0001), least bias (-3 ml/min), and best precision (16 ml/min) between thermodilution and echocardiographic methods were obtained at the level of aortic annulus using pulsed Doppler. In conclusion, CO could be accurately assessed in rats using TTE and pulsed Doppler at the level of the aortic annulus. This annulus was demonstrated to remain stable, but pulmonary annulus, thoracic aorta, mitral valve, and left ventricular diameters were found to be more modifiable during volumic changes.
Animals↗
Respiratory variations of aortic VTI: a new index of hypovolemia and fluid responsiveness.
In 12 mechanically ventilated and anesthetized rabbits, we investigated whether the magnitude of respiratory changes in the aortic velocity time integral (VTI(Ao)), recorded by transthoracic echocardiography (TTE) during a stepwise blood withdrawal and restitution, could be used as a reliable indicator of volume depletion and responsiveness. At each step, left and right ventricular dimensions and the aortic diameter and VTI(Ao) were recorded to calculate stroke volume (SV) and cardiac output (CO). Respiratory changes of VTI(Ao) (maximal - minimal values divided by their respective means) were calculated. The amount of blood withdrawal correlated negatively with left and right ventricular diastolic diameters, VTI(Ao), SV, and CO and correlated directly with respiratory changes of VTI(Ao). Respiratory VTI(Ao) variations (but not other parameters) at the last blood withdrawal step was also correlated with changes in SV after blood restitution (r = 0.83, P < 0.001). In conclusion, respiratory variations in VTI(Ao) using TTE appear to be a sensitive index of blood volume depletion and restitution. This dynamic parameter predicted fluid responsiveness more reliably than static markers of cardiac preload.
Animals↗
Diastolic dysfunction in hypertension.
Heart failure is one of the most common causes of cardiovascular morbidity and mortality, and hypertension is the most common cause of cardiac failure. Recent studies have shown that isolated diastolic dysfunction very often accompanies hypertensive heart disease. Ventricular diastolic function may be divided into an active relaxation phase and a passive compliance period. These two components have been investigated invasively, and they remain the gold standards for the study of diastolic function. However, in the routine clinical setting, echocardiographic and Doppler techniques are most useful for evaluating ventricular filling. Thus, analysis of E and A waves of mitral flow have provided important and useful information. Unfortunately, these indices depend on too many factors. Newer indices obtained from ventricular time intervals, tissue Doppler imaging, and color M-mode echocardiography have enhanced the means to assess diastolic function. In addition, new methods including MRI and cine CT have also provided better understanding of left ventricular filling in hypertension. Using these techniques, diastolic dysfunction has been found to be common in patients with hypertension, even before left ventricular hypertrophy is demonstrable and before hypertension in young, normotensive male offspring of hypertensive parents has developed. Furthermore, it has been made clear recently that myocardial ischemia and fibrosis are two important factors associated with diastolic dysfunction in hypertension.
Diastole↗
Prevention of hypertension.
Hypertension is a major risk factor for many cardiovascular diseases including stroke, coronary heart disease, cardiac failure, and endstage renal disease. Therefore, prevention of hypertension becomes an important goal in overall efforts to control blood pressure and reduce the incidence of hypertension-related cardiovascular and renal complications and outcomes. Many risk factors underlying hypertension have been identified including nonmodifiable factors such as age, gender, genetic factors, and race, as well as modifiable factors including overweight, high sodium intake, low potassium intake, alcohol consumption, and reduced physical activity. A number of studies have demonstrated that interventions aimed at changing these modifiable factors might decrease blood pressure and even prevent the development of hypertension. Thus, present national recommendations and guidelines include lifestyle modifications ranging from weight loss in case of obesity, engagement in regular isotonic physical activity, reduced sodium diet (<100 mmol/d), supplementation of potassium, and alcohol moderation (<1 ounce of ethanol or its equivalent per day).
Aging↗