Pressor Factors Research Articles

Elderly Patient with Hypertension in General Practice: Clinical Features and Antihypertensive Therapy

The prevalence of arterial hypertension (AH) increases with age: among people over 60 years old this index is more than 2 times higher in the general population, 2/3 of people over 65 years old suffer from hypertension. Among patients 65–89 years old with hypertension, 2/3 patients have isolated systolic hypertension (ISAG). Features of hypertension in the elderly patients are: lability of blood pressure (BP), increasing frequency of pseudohypertension, high frequency of «white coat hypertension», decreased sensitivity of pressor factors for antihypertensive drugs, high frequency of resistant to treatment of hypertension. The new recommendations of the European Society of Cardiology for the diagnosis and treatment of hypertension emphasize 2 groups of elderly patients: 65–79 years old and ≥80 years old, which described the epidemiological features, the prevalence of risk factors for cardiovascular events, blood pressure levels for antihypertensive therapy and target blood pressure, and the recommended principles of drug therapy that are different from young and middle-aged patients. For most patients, fixed combinations are indicated as starting AGT, but monotherapy is recommended for the treatment of hypertension in very elderly patients (over 80 years old) and elderly patients over 65 years old with senile asthenia. The decreasing of blood pressure should be gradual, taking into consideration the increased risk of orthostatic reactions at this age. European and American experts recommend os first-line drugs low doses of thiazide diuretics and calcium channel antagonists (mainly dihydropyridine), which are especially indicated in isolated systolic arterial hypertension to effectively reduce the frequency of cardiovascular complications in the treatment of elderly patients with hypertension.

Stress and catecholamines.

Stress and catecholamines.

Role of limbic peptidergic circuits in regulation of arterial pressure, relevant to development of essential hypertension

It is generally accepted that the essential hypertension (EH) is caused by interactions among congenital gene, multiple pathogenetic pressor factors, and disorder of physiologic depressor factors. The central nervous system may play a key role in the development of EH. The underlying mechanisms, however, are not well understood. Studies show that peptidergic transmitters in the limbic forebrain are involved in long-term regulation of arterial pressure and in the pathogenesis of EH. In the limbic forebrain there are peptidergic pressor and depressor circuits. The former includes corticotropin releasing factor-, substance P-, and angiotensin II-circuits; and the latter includes beta-endorphin- and atrial natriuretic peptide-circuits. These circuits extensively interconnect and interact with each other. The altered functions of them may be the pathogenesis of EH. In this review, we focus on the roles of limbic peptidergic circuits in regulation of arterial pressure, relevant to the neurogenetic mechanisms in developing EH.

Obesity and hypertension: from pathophysiology to treatment.

While the prevalence of hypertension is clearly increased among the overweight persons, the pathophysiological mechanisms underlying this frequent association of obesity and hypertension are still poorly understood. The expansion of extracellular volume, inducing hypervolaemia and increased cardiac output, represents the characteristic haemodynamic feature of the obesity-related hypertension. The maintenance of hypervolemia in the face of elevated blood pressure, indicates a resetting of pressor natriuresis toward higher blood pressure. The development of hypertension also indicates an increase in peripheral vascular resistance, thus the lack of physiological adaptation of peripheral resistance to increased cardiac output. The mechanisms underlying these changes in renal function and vascular reactivity can no longer be attributed to hyperinsulinaemia as such, but might be related to insulin resistance responsible for the enhancement in pressor activity of noradrenaline and angiotensin II. This increased reactivity to pressor factors may be due to an inadequate nitric oxide generation by vascular endothelium and to increased sodium and calcium concentration in vascular smooth muscle cells. The role of increased neuropeptide Y (NPY) activity, may also be involved. As to enhancement of tubular sodium reabsorption, it could be related to histological changes within the renal medulla, leading to compression of tubules and vasa recta, hence a more efficient sodium reabsorption. As to the therapeutic approach, the low-energy sodium-restricted diet associated with increased physical activity, represents the cornerstones of treatment for the obesity-related hypertension. If this approach fails, the pharmacological treatment becomes necessary, and the use of the converting enzyme inhibitors seems to be the most appropriate choice of drug therapy for hypertensive obese patients.

D90 Blood pressure elevation from the great Hanshin earthquake — Analysis of pressor factors and effects of antihypertensive agents

D90 Blood pressure elevation from the great Hanshin earthquake — Analysis of pressor factors and effects of antihypertensive agents

Seasonal differences in diurnal blood pressure of hypertensive patients living in a stable environmental temperature

To determine whether there is a seasonal variation in blood pressure in hypertensive patients whose daily lifestyle is similar in summer and in winter, and who live almost entirely indoors in a stable environmental temperature. During summer and winter, blood pressure was measured by ambulatory blood pressure monitoring in outpatients with essential hypertension, and environmental temperature was measured by electrothermometer while the patients were awake. The 24-h blood pressure data were analysed after being divided into four groups: morning, afternoon, night-time and sleeping periods. We studied 25 outpatients (mean +/- SD age 57 +/- 12 years) who spend virtually the entire day indoors in both summer and winter. Measurements of systolic and diastolic blood pressure in the morning and night-time periods were significantly higher in winter than in summer (differences of 7.5 +/- 14.7 and 4.1 +/- 8.8 mmHg and 8.2 +/- 14.8 and 4.5 +/- 8.1 mmHg, respectively). Blood pressure measured in the afternoon and during sleeping periods did not differ significantly. No correlation was observed between the seasonal change in blood pressure in the morning and that at night. Environmental temperatures were significantly higher in the morning, afternoon and night-time periods during summer than those during winter. The differences among these periods were not statistically significant. There is a seasonal variation in blood pressure in the morning and night-time periods during winter in hypertensive patients who live essentially indoors in a relatively stable environmental temperature. Pressor factor(s) may differ between morning and night-time periods during winter.

Insulin resistance and hyperinsulinemia in hypertension.

GENETIC PREDISPOSITION: Insulin resistance and reactive hyperinsulinemia occur not only with obesity, impaired glucose tolerance or non-insulin-dependent (type 2) diabetes mellitus, but also in many non-obese, non-diabetic patients with essential hypertension and their currently normotensive, lean, young offspring, as well as in some other conditions known to promote hypertension. Insulin resistance impairs glucose tolerance, while insulin resistance and/or hyperinsulinemia promote dyslipidemia, body fat deposition and probably atherogenesis. Therefore, the common coexistence of a genetic predisposition for hypertension with insulin resistance helps to explain the frequent, although temporally often dissociated, occurrence of hypertension together with dyslipidemia, obesity and type 2 diabetes in a given patient. INSULIN RESISTANCE AND HYPERINSULINEMIA AS SLOW PRESSOR MECHANISMS: In the pathogenesis of hypertension, inappropriate vasoconstriction (due to an imbalance of vasoactive substances and/or raised cytosolic calcium) and/or structural vasculopathy is particularly important. Among the mosaic of assumed pressor mechanisms, distinct Na+ retention is almost invariably involved in diabetes mellitus, while sympathetic activation tends to occur in essential hypertension, particularly in association with obesity. Insulin resistance may develop as a consequence of an intracellular excess of Ca2+ or a decrease in Mg2+, an impaired insulin-mediated rise in skeletal muscle blood flow, increased sympathetic activity or excess body weight. Acute hyperinsulinemia causes arterial vasodilation on one hand and increases sympathetic activity and renal Na+ reabsorption on the other. Chronically, hyperinsulinemia may promote cardiovascular muscle cell proliferation and atherogenesis, while insulin resistance may be associated with certain transmembraneous cation transporters, leading to an increase in cytosolic Ca2+. Hyperinsulinemia and/or insulin resistance may also be associated with an increased blood pressure sensitivity to high salt intake. In the mosaic of many different blood pressure-raising mechanisms, insulin resistance and/or hyperinsulinemia is likely to represent an amplifying slow or very slow pressor factor.

Parathyroid hypertensive factor-like activity in human essential hypertension

To determine the clinical relevance of the newly described circulating pressor factor with parathyroid hypertensive factor (PHF)-like activity. Plasma samples were collected from 94 normotensive and 93 essential hypertensive subjects, the latter either previously defined by dietary salt sensitivity (n = 43), or prospectively studied on both low- (< 50 mmol/day) and high-salt (> 200 mmol/day) diets (n = 16). Blood pressure, demographic factors, plasma renin activity (PRA), urinary electrolyte excretion and bioassayable PHF-like activity were determined in the fasted state on basal and altered dietary salt intakes. Among the normotensive subjects significantly higher PHF-like activity and reciprocally lower PRA values were observed in Black versus Caucasian subjects, particularly among females. In the hypertensive subjects PHF-like activity levels were significantly elevated in the low- (17.1 +/- 1.5 mmHg, n = 34) and normal- (6.7 +/- 1.8 mmHg, n = 36) but not in the high-renin subgroups compared with values in the normotensive subjects (1.6 +/- 1.1 mmHg). Similarly, PHF-like activity values were significantly higher in salt-sensitive than in salt-insensitive hypertensives. Prospectively, PHF-like activity rose significantly with salt loading (4.9 +/- 1.2 to 20.4 +/- 6.2 mmHg) and was positively related (r = 0.648, P < 0.001) to the pressor response to salt. Elevated levels of PHF-like activity are characteristic of the low-renin or salt-sensitive state, or both, and may contribute to the hypertensive process. Elevated PHF-like activity levels found in normotensive subjects may presage the development of low-renin, salt-sensitive hypertension.

Hypertension and exercise.

A sedentary lifestyle may be a risk for hypertension, according to the results of both cross sectional and longitudinal studies. However, exercise may reverse the adverse effects of lack of activity. Many controlled studies have shown that exercise lowers systolic/diastolic blood pressure by at least 10/5 mmHg. Exercise not only improves blood pressure, but also attenuates other risk factors for cardiovascular complications. Dynamic isotonic exercise (e.g., weight lifting). Milder (e.g., brisk walking for 30-60 minutes/day) rather than moderate to severe exercise (e.g., running) is also recommended because of similar effectiveness and better compliance. The underlying mechanism of action of exercise on blood pressure seems to be multifactorial involving a decrease in pressor factors such as plasma norepinephrine, the serum Na/K ratio, endogenous ouabain-like substance and erythrocyte mean corpuscular volume, as well as an increase in depressor factors such as plasma prostaglandin E, serum taurine and urinary dopamine excretion.

Correlation of Blood Pressure in End-Stage Renal Disease with Platelet Cytosolic Free Calcium Concentration during Treatment of Renal Anemia with Recombinant Human Erythropoietin

The hemodynamic hallmark of hypertension complicating the treatment of renal anemia with recombinant human erythropoietin (rHu-EPO) is increased total peripheral vascular resistance, but the mechanisms underlying the arteriolar vasoconstriction are still an enigma. We studied body fluid volumes, plasma renin activity, plasma norepinephrine, and calcium metabolism in platelets in 40 previously normotensive hemodialysis patients before and after 12 weeks of rHu-EPO treatment. Partial correction of anemia caused a rise in arterial pressure (94 +/- 6 mmHg vs 124 +/- 7 mmHg, p less than 0.05) and in platelet cytosolic calcium concentration (113 +/- 5 nM vs 171 +/- 18 nM, p less than 0.05) in eight patients. Hypertensive patients had significantly higher plasma noradrenaline concentrations, but they did not differ significantly in body fluid volumes and plasma renin activities. There was a close correlation between free calcium concentration in platelets and mean arterial pressure in patients developing rHu-EPO-induced-hypertension (r = 0.95). Short-term antihypertensive treatment resulted in a reduction of free calcium concentrations in platelets and a concomitant fall in blood pressure. The main results of the present studies suggest that rHu-EPO-induced hypertension might be associated with altered cellular calcium homeostasis and hyperactivity of the sympathetic nervous system. If rHu-EPO therapy induces alterations of pressor factors or the hormone itself raises the cytosolic calcium not only in platelets but also in vascular smooth muscle cells, altered cellular calcium influx may contribute to the arteriolar vasoconstriction.

Is Heart Failure an Abnormality of Myocardial Cell Growth?

The evolution of our understanding of the pathogenesis and therapy of heart failure can be described in terms of three paradigms that have also proven useful in describing the development of knowledge of cardiovascular regulation and the actions of angiotensin II. Organ physiology, the first paradigm, viewed the variable performance of the heart in terms of length-dependent changes in myocardial contractile function (Starling's Law), and angiotensin II as a pressor factor that elevated blood pressure. This paradigm focused treatment of heart failure on the major circulatory abnormalities: salt and water retention and vasoconstriction. According to the second paradigm, cell biochemistry, regulation of cardiac performance reflected altered calcium fluxes and changing myocardial contractility, and the clinical effects of angiotensin II as arising from altered calcium fluxes involved in the control of smooth muscle tension. Following this second paradigm, treatment of heart failure focused on powerful inotropic agents designed to increase myocardial contractility. The third paradigm, gene expression (molecular biology) describes what is probably the most primitive, and almost certainly the most complex of these regulatory mechanisms. Altered gene expression explains long-term regulation of cardiac performance in terms of adaptive changes in the architecture and composition of the heart, and key effects of angiotensin II as arising from increased protein synthesis and promotion of cell growth. In the case of heart failure, this third paradigm may explain the accelerated deterioration of the hypertrophied, failing heart as being due to altered myocardial cell growth composition. While the useful life of the normal human heart appears to be at least 80-90 years, overload-induced hypertrophy may reduce the heart's life span to about 5 years. This unwelcome consequence of myocardial hypertrophy may arise from the expression of fetal isoforms of key muscle proteins, a hypothesis that is supported by evidence that deterioration of the failing heart can be alleviated by the converting enzyme inhibitors which have important effects to inhibit cellular growth.

Renal excretion of arginine-vasopressin in microalbuminuric diabetic patients.

Enhanced activity of haemodynamic hormones have been reported to be involved in the development of renal lesions of diabetic kidney1,2. Apart from other pressor factors even plasma arginine-vasopressin (AVP) have been found to be increased in uncontrolled diabetic patients very probably reflecting both a hypovolemic status and an increase in “effective” extracellular fluid osmolality; however, high circulating AVP levels have also been observed in certain well controlled diabetic patients thus suggesting that an alteration of mechanisms regulating AVP secretion exists in diabetes mellitus3,4.

Mechanisms of pressor responses to intracisternal administration of hypertonic NaCl in conscious, unrestrained normotensive and spontaneously hypertensive rats.

We evaluated the mechanisms of pressor responses to hypertonic NaCl administered intracisternally (IC) to conscious normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Both mean arterial pressure (MAP) and heart rate (HR) increased immediately after IC NaCl (1.5mol/l, 60 microliters/kg), but MAP returned rapidly to the basal level. Pressor and tachycardic actions at the early phase were mostly abolished by either hexamethonium or phentolamine with the blockade of sympathetic nervous system (SNS), and slightly diminished by the V1-vasopressin blocker. In contrast, at the following phase pressor responses were not suppressed by combined or solitary blockade of SNS, vasopressin and angiotensin II (AII). The pressor effects of IC NaCl were slightly greater in SHR than in WKY. It is concluded that the early-phase increases in MAP by hypertonic NaCl administered IC to conscious SHR and WKY may be attributed mainly to the increased activity of SNS and partly to the increased release of AVP, although the late- phase pressor responses may result from some pressor factor(s), unrelated to SNS, AVP and AII.

Changes in vascular endothelium and its function in systemic arterial hypertension

The various functions of arterial endothelium may be altered during pulmonary and arterial hypertension. Changes in the endothelium (or function) associated with hypertension are described. In both acute and chronic hypertension, permeability of the endothelium is enhanced. During the acute phase of hypertension, hyperplasia (cell replication) of the endothelium occurs while cell hypertrophy (enlarged cell size) and an increase in homocellular tight junctions are associated with sustained elevations of blood pressure. Endothelium may contribute to the increase in smooth muscle mass or cell number reported with various models of hypertension. Increased endothelial uptake or metabolism of norepinephrine and serotonin occurs during hypertension. The biotransformation of adenine nucleotides and various peptides by the endothelium is not altered by hypertension. Synthesis of prostacyclin is enhanced in the spontaneously hypertensive and Goldblatt hypertensive rat. Metabolism of prostaglandin E 2, prostaglandin F 2α and prostacyclin by prostaglandin 15-hydroxydehydrogenase is impaired in the genetic models. Responses to endothelium-dependent vasodilators are impaired in acute and chronic models of hypertension. Production of relaxing factor by the endothelium is not inhibited, but rather the vascular smooth muscle fails to respond. Acute, severe hypertension potentiates the response to serotonin, presumably by attenuating the release or response to relaxing factor(s). In the aorta of the spontaneously hypertensive rat, the endothelium releases a constricting factor in response to acetylcholine. Pulmonary arterial endothelium (and other vessels) releases a vasoconstrictor that is blocked by inhibitors of cyclooxygenase. It is not clear whether this pressor factor is thromboxane A 2. Cultured endothelial cells release a polypeptide that contracts arteries; however, any relation to hypertension is not known.

Pressor factors and responsiveness in hypertension accompanying diabetes mellitus.

Hypertension accompanying diabetes mellitus may involve abnormalities in at least two major blood pressure-regulating systems: the body sodium-fluid volume state and cardiovascular reactivity. In metabolically stable nonazotemic diabetes, exchangeable sodium is increased by 10% on average, regardless of age, insulin dependence or nondependence, or the presence or absence of diabetic retinopathy or clinical nephropathy (proteinuria greater than or equal to 0.3 g/24 hr). Possible contributing mechanisms include renal sodium retention and an extravascular shift of fluid and sodium; intracellular accumulation is not excluded. Circulatory volume is normal or low and the total exchangeable sodium/blood volume ratio increased. In hypertensive diabetes, the latter abnormality is particularly pronounced; systolic pressure tended to correlate with exchangeable sodium (r = 0.47, p less than 0.001) and diastolic pressure with the plasma sodium/potassium ratio (r = 0.25, p less than 0.05). Plasma aldosterone, renin, epinephrine, and norepinephrine levels are generally normal or sometimes low in metabolically stable nonazotemic diabetic patients with normal or high blood pressure; the plasma clearance of norepinephrine also appears to be unaltered. The cardiovascular pressor responsiveness to norepinephrine is often exaggerated relative to concomitant plasma concentrations, regardless of age, type of antidiabetic treatment, or presence or absence of diabetic retinopathy, peripheral neuropathy, or high blood pressure. Pressor responsiveness to angiotensin II also may sometimes be increased relative to plasma renin levels. Sodium retention and diabetic vasculopathy of resistance vessels could be important complementary mechanisms of hyperreactivity. In diabetes with mild hypertension, diuretic treatment restored exchangeable sodium, norepinephrine pressor responsiveness, and blood pressure toward normal. Thus sodium retention and cardiovascular hyperreactivity tend to occur even at the normotensive, nonazotemic stage of diabetes and may concomitantly predispose for the frequent development of hypertension in the diabetic population.

Gamma linolenic acid attenuates cardiovascular responses to stress in borderline hypertensive rats.

The purpose of the present study was to investigate the effects of gamma linolenic acid (GLA) on cardiovascular responses to psychosocial stress (isolation) and to pressor hormones in the genetically borderline hypertensive rat (SHR X WKY). Adult male SHR X WKY were divided into two groups following five weeks of group housing. One group (GLA) received eight weeks constant flow osmotic pumps releasing 0.04 mg GLA in olive oil/kg-hr, while the second group received dummy pumps (DUM). One week following pump implantation, each group was divided into two subgroups and exposed to a four-week experimental period of either continued group housing (no stress) or isolation (stress). A two-week recovery period of group housing followed the experimental period. Blood pressure and heart rate were determined weekly by the tail cuff technique. At the end of the recovery period, animals in the no stress condition were anesthetized and received an arterial cannula for NOR and ANG infusion and direct BP recording. Then the responses to an ED50 of NOR and ANG were determined. All animals were then killed for determination of heart weight and adrenal weight. All groups had mean control period systolic BP values ranging from 143-146 mm Hg. In the no stress condition, neither GLA nor DUM altered BP over the course of the study. However, BP increased in the DUM group during all four weeks of the isolation period vs the control period (p less than 0.01), whereas BP increased only in week 1 in the GLA group (p less than 0.05). Heart rate increased during stress in the DUM group (p less than 0.05), but not in the GLA group. Vascular reactivity to NOR was unaffected by GLA administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac substances that influence blood-pressure II. Potent pressor activity in rat and rabbit atrial muscle

In addition to their natriuretic, diuretic and vasodilator activities, freshly prepared aqueous extracts of either rat or rabbit atrial myocardium were shown to elicit significant increases in the blood-pressure of anaesthetized rats. Small aliquots (0.05 mℓ) intravenously administered caused a transient rise in mean arterial blood-pressure of up to 20%. Slow infusion of 0.4 mℓ right atrial extract (corresponding to about one half of a rabbit right atrial lobe) during 90 seconds caused the expected natriuresis and diuresis, together with a sustained elevation in arterial blood-pressure ( ca 25%) that returned to normal within 3 minutes. This potent pressor activity could not be detected in ventricular extracts. It was furthermore readily separable from the natriuretic peptides and catecholamines by ultrafiltration. The atrial pressor factor is a small proteolytically unstable molecule (300 – 1000 dalton).

Renin, angiotensin II, aldosterone, catecholamines, prostaglandins and vasopressin. The importance of pressor and depressor factors for hypertension in pregnancy.

Renin, angiotensin II, aldosterone, catecholamines, prostaglandins and vasopressin. The importance of pressor and depressor factors for hypertension in pregnancy.

Role of Adrenergic Overactivity and Pressure Overload in the Pathogenesis of Left Ventricular Hypertrophy in Borderline and Sustained Essential Hypertension in Man

1. In 16 borderline and 18 sustained hypertensive patients, interventricular septal thicknesses (by echocardiography) were greater than those found in 18 healthy subjects. Values in borderline and sustained hypertensives did not differ significantly. 2. In healthy subjects and borderline hypertensive patients, posterior wall thicknesses were normal, whereas they were greater in sustained hypertensive patients than in the former two groups. 3. In borderline hypertension, interventricular septal thickness was positively correlated with resting supine (r = 0.89, P &amp;lt; 0.001) as well as upright (r = 0.60, P &amp;lt; 0.01) plasma noradrenaline, but not with adrenaline, plasma renin activity and mean blood pressure. 4. In sustained hypertension, posterior wall thickness was positively correlated with mean blood pressure (r = 0.85, P &amp;lt; 0.001), but not with noradrenaline, adrenaline and plasma renin activity. 5. In human hypertension, left ventricular hypertrophy seems to involve only the interventricular septum in the borderline stage, extending to the posterior wall in the sustained stage. Adrenergic overactivity could play an important role in development of interventricular septal hypertrophy in borderline hypertension, whereas pressor factors could be mainly involved in the development of posterior wall hypertrophy in sustained hypertension.

Vasopressin: An essential pressor factor for blood pressure recovery following hemorrhage

Two experimental approaches were used to evaluate the importance of the pressor effects of vasopressin in blood pressure recovery following hypotensive hemorrhage. Experiments using homozygous Brattleboro rats demonstrated that the hemodynamic recovery of these animals was subnormal, even though the activation and efficacy of the sympathetic nervous and renin-angiotensin systems were intact. Experiments using an antipressor vasopressin analogue in normal rats during hypotensive hemorrhage demonstrated significantly blunted blood pressure recovery in the presence of the analogue. Thus, both experiments indicate that the pressor effects of circulating vasopressin play an essential role in blood pressure recovery following hypovolemic hypotension induced by hemorrhage.