Predictors of perioperative complications in paediatric cranial vault reconstruction surgery: a multicentre observational study from the Pediatric Craniofacial Collaborative Group.

BACKGROUND: The current incidence of major complications in paediatric craniofacial surgery in North America has not been accurately defined. In this report, the Pediatric Craniofacial Collaborative Group evaluates the incidence and determines the independent predictors of major perioperative complications using a multicentre database. METHODS: The Pediatric Craniofacial Surgery Perioperative Registry was queried for subjects undergoing complex cranial vault reconstruction surgery over a 5-year period. Major perioperative complications were identified through a structured a priori consensus process. Logistic regression was applied to identify predictors of a major perioperative complication with bootstrapping to evaluate discrimination accuracy and provide internal validity of the multivariable model. RESULTS: A total of 1814 patients from 33 institutions in the US and Canada were analysed; 15% were reported to have a major perioperative complication. Multivariable predictors included ASA physical status 3 or 4 (P=0.005), craniofacial syndrome (P=0.008), antifibrinolytic administered (P=0.003), blood product transfusion >50 ml kg-1 (P<0.001), and surgery duration over 5 h (P<0.001). Bootstrapping indicated that the predictive algorithm had good internal validity and excellent discrimination and model performance. A perioperative complication was estimated to increase the hospital length of stay by an average of 3 days (P<0.001). CONCLUSIONS: The predictive algorithm can be used as a prognostic tool to risk stratify patients and thereby potentially reduce morbidity and mortality. Craniofacial teams can utilise these predictors of complications to identify high-risk patients. Based on this information, further prospective quality improvement initiatives may decrease complications, and reduce morbidity and mortality.

Cardiac regression and blood pressure control in the Dahl rat treated with either enalapril maleate (MK 421, an angiotensin converting enzyme inhibitor) or hydrochlorothiazide.

Enalapril maleate (MK 421), and hydrochlorothiazide were used to evaluate the control of hypertension and reversal of myocardial hypertrophy in Dahl sensitive (DS) and Dahl resistant (DR) rats given either a high (8% NaCl) or a low salt (0.4% NaCl) diet. Groups of six-week-old male DS and DR rats were treated with enalapril (15-100 mg/kg/day) in drinking water for eight weeks. Additional comparable groups of DS and DR were also treated with hydrochlorothiazide (60-400 mg/kg/day). Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and heart weight/body weight (Hwt/Bwt) ratio were determined. We observed significant reduction in Hwt/Bwt ratio (P less than 0.001) along with control of SBP and DBP in the DS given a high salt diet treated with either enalapril or hydrochlorothiazide. However, in the DR given a high salt diet, cardiac regression (Hwt/Bwt ratio, P less than 0.05), SBP and DBP (P less than 0.01) reduction were seen only with enalapril. Similarly, cardiac regression (Hwt/Bwt ratio, P less than 0.05) was observed along with reduction of SBP and DBP (P less than 0.001) in the DS given a low salt diet and DR given enalapril. These data indicate that enalapril reduced SBP and DBP in association with cardiac regression in hypertensive and normotensive rats. In contrast, hydrochlorothiazide only reduced SBP, DBP and caused cardiac reversal (Hwt/Bwt ratio) in DS placed on a high salt diet.

Separation of essential hypertensive patients based on blood pressure responses after the withdrawal of antihypertensive agents by step-wise discriminant analysis.

Thirty-five patients with uncomplicated hypertension were observed for blood pressure behaviour after prolonged antihypertensive medication withdrawal. Twenty-three patients (Group 1) remained normotensive (systolic less than 140 mmHg, diastolic less than 95 mmHg) for over 60 weeks compared to 12 patients (Group 2) who became hypertensive again during a 4-week placebo period. Discriminant analysis was performed on 31 clinical and laboratory variables measured before therapy to separate any discriminating factors for the two groups. Four variables maximized the separation of Group 1 from Group 2 patients. In descending order, these were serum sodium (p less than 0.001), mean corpuscular volume (p less than 0.01), serum albumin (p less than 0.01), and body weight (p less than 0.05). Using these four variables 73.9% of patients in Group 1 and 75% of patients in Group 2 were classified correctly into their respective groups. It is suggested that this observation may be useful in the development of new therapeutic regimens for patients with uncomplicated essential hypertension, for example by predicting those patients who may respond favourably to intermittent therapy or even to its withdrawal.

Left ventricular changes after chronic therapy with enalapril maleate in moderate to severe hypertensive patients.

A randomized double-blind trial was carried out to determine the relationship of the changes in blood pressure and heart rate with changes in echocardiographic left ventricular indices in moderate to severe hypertensive patients with established left ventricular hypertrophy who were being treated chronically with enalapril or hydrochlorothiazide plus propranolol for 26 weeks. After a 2-week period on placebo, drug dosages in the two groups were adjusted to individual needs until blood pressure was normalized (diastolic less than 90 mmHg). Patients in Group I received 10 to 40 mg enalapril/day; those in Group II received 50 mg hydrochlorothiazide plus 80 to 240 mg propranolol/day. Echocardiographic measurements were made at the end of the placebo and 26-week active treatment periods. Significant correlations were observed between the changes in four pairs of variables in each group. In the 8 patients receiving enalapril, there were negative correlations between interventricular septal thickness and supine systolic blood pressure, erect and supine heart rates, and a positive correlation between relative wall thickness and erect diastolic blood pressure. In the 7 patients on hydrochlorothiazide plus propranolol, there were negative correlations between relative wall thickness and erect and supine heart rate, and positive correlations between left ventricular mass and erect diastolic blood pressure, and the percentage change in internal diameter of the left ventricle and supine systolic blood pressure. Possible explanations for and implications of these regional changes are discussed.

The correlation of changes in systolic blood pressure with regional anatomical regression of hypertensive left ventricular hypertrophy in patients on chronic antihypertensive therapy (greater than 1 year): alpha-methyldopa compared to propranolol.

Twenty patients with mild to moderate hypertension and evidence of left ventricular hypertrophy (relative wall thickness greater than or equal to 0.45), who previously had not received either alpha-methyldopa or propranolol, were allocated at random to treatment with one or other of these drugs as monotherapy after a 2-week baseline period on no medication. Dosage was titrated until normotension was attained and patients were then maintained on this treatment for a year. Analysis of blood pressure measurements and echocardiograms taken before and during maintenance therapy showed that there were significantly correlated changes in systolic blood pressure and heart rate with left ventricular cavity and regional wall changes during chronic drug administration. In the alpha-methyldopa group there were significant correlations between changes in erect and supine systolic blood pressure and the posterior wall index, and in erect systolic blood pressure and left ventricular mass. In the propranolol group, there were significant correlations between changes in supine systolic blood pressure and interventricular septal thickness, and in erect heart rate and supine systolic blood pressure with the percentage change in internal diameter of the left ventricle. It is suggested that these observations may have important therapeutic implications for hypertensive patients with documented left ventricular hypertrophy.

Potassium conservation with amiloride/hydrochlorothiazide ("Moduret') in thiazide-induced hypokalaemia in hypertension.

A double-blind study was carried out in 24 hypertensive patients with thiazide-induced hypokalaemia (serum potassium less than 3.2 mmol/l) to compare the effects of treatment with an amiloride/hydrochlorothiazide combination or hydrochlorothiazide alone. The study was divided into three phases: (i) potassium repletion (Weeks 0 to 4) with oral potassium chloride (40 mmol/day), (ii) stabilization (Weeks 4 to 6) of normokalaemia, and (iii) active drug treatment (Weeks 6 to 14), patients being allocated at random to receive one or other of the two treatments. Dosage was 2 tablets per day of the 5 mg amiloride plus 50 mg hydrochlorothiazide combination or of 50 mg hydrochlorothiazide alone. The results showed that blood pressure control was comparable in both treatment groups but hydrochlorothiazide alone caused a statistically significant reduction in serum potassium levels compared to the drug combination. Apart from 1 patient who developed hypokalaemia on hydrochlorothiazide alone, no other side-effects of treatment were reported.

Converting enzyme inhibition attenuates the noradrenaline response to the Valsalva maneuvre.

HYPOTHESIS: Reduction of plasma angiotensin II inhibits release of noradrenaline in response to a sympathetic nervous system stimulus. OBJECTIVE: To compare heart rate and plasma catecholamine responses to the Valsalva maneuvre before and after inhibition of angiotensin converting enzyme. DESIGN: Four weeks of placebo (all patients). If sitting diastolic blood pressure was found to be between 100 and 115 mmHg, then double-blind randomization to receive 2.5, 5, 10 or 20 mg of quinapril bid for a further four weeks. SETTING: Ambulatory hypertension clinic with admission to clinical investigation unit overnight for interventions. PATIENTS: Uncomplicated essential hypertensives of English-Irish ancestry. Twenty-five eligible patients completed the study, while three additional patients withdrew early. INTERVENTIONS: Blood pressure and heart rate were monitored weekly during placebo, and biweekly during active treatment. Patients were rehearsed in performance of the Valsalva maneuvre. At the end of the placebo and active therapy phases, each patient performed standard Valsalva maneuvres immediately before and 2 h after the morning dose of placebo or active drug. Heart rate was recorded continuously throughout the maneuvre, while blood was sampled for catecholamine determinations prior to the start of straining and again approximately 10 s following the end of straining. MAIN RESULTS: Heart rate responses to the Valsalva maneuvre were not affected by acute administration of quinapril, but a slight attenuation of the tachycardic response was seen after four weeks of therapy (P less than 0.05). An increase in plasma noradrenaline concentration associated with the straining phase of the Valsalva maneuvre was markedly attenuated after both acute and chronic quinapril therapy (P less than 0.01). CONCLUSION: By blocking biosynthesis of angiotensin II, converting enzyme inhibition may attenuate baroreceptor-stimulated release of noradrenaline.

The pharmacodynamic responses of hypertensive patients to quinapril therapy.

HYPOTHESIS: Impaired baroreflex-induced release of noradrenaline during angiotensin converting enzyme (ACE) inhibition may interfere with orthostatic responses of blood pressure. OBJECTIVE: To compare blood pressure and heart rate responses of hypertensive patients to upright posture over a 12 h period before and after quinapril therapy. DESIGN: Four weeks of placebo was given to all patients. If subject's sitting diastolic blood pressure was between 100 and 115 mmHg, patients received 2.5, 5, 10 or 20 mg quinapril bid for four more weeks in a double-blind randomized fashion. SETTING: Ambulatory hypertension clinic with admission to clinical investigation unit overnight for interventions. PATIENTS: Uncomplicated essential hypertensives of English or Irish ancestry. Twenty-five eligible patients completed the study while three withdrew early. INTERVENTIONS: Supine and erect blood pressures and heart rates were recorded for each patient at 1 to 2 h intervals over a 12 h period following ingestion of placebo capsule and again after initial acute dose of quinapril the next day. Blood was sampled for quinapril and quinaprilat concentrations. Procedure was repeated after four weeks of quinapril therapy following morning dose of drug. MAIN RESULTS: Orthostatic response of diastolic pressure was reduced while maintenance of systolic was impaired 1 to 4 h following an acute dose of quinapril. Orthostatic cardioacceleration was maintained. Responses were largely restored after four weeks of chronic therapy. CONCLUSIONS: A possible initial impairment of baroreflex-mediated peripheral vasoconstriction by ACE inhibition may be offset by compensatory changes to vascular reactivity.

The blood pressure responses of thiazide-resistant hypertensives to a once-a-day bevantolol regimen.

The antihypertensive efficacy of a single daily dose of bevantolol (200 mg) alone or in combination with hydrochlorothiazide (25 mg) has been compared against conventional twice daily propranolol (80 mg) therapy in a group of 22 hypertensive patients whose blood pressures did not respond to thiazide monotherapy. Addition of bevantolol to the diuretic resulted in a significant (P less than 0.001) fall in sitting blood pressures (144/97 to 137/90 mmHg), supine blood pressures (147/100 to 141/92 mmHg) and heart rate (83 to 73 beats/min) 24 h after administration. When the diuretic was withdrawn, heart rate and diastolic pressures remained unchanged and within normotensive limits but systolic pressures increased to pre-treatment levels. Substitution of propranolol for bevantolol gave results comparable to the combined bevantolol-diuretic regimen except that heart rate was still lower (66 beats/min). No significant adverse reactions were reported. In thiazide-resistant hypertensives, a once daily dose of 200 mg bevantolol effectively reduced diastolic blood pressures towards normotensive limits and to an extent comparable with twice daily propranolol therapy.

Correlation of forearm vascular and catecholamine responses of hypertensive patients to baroreceptor stimulation.

The relationship between changes in forearm vascular hemodynamics and plasma catecholamine levels during the performance of the Valsalva maneuvre by pretrained hypertensive patients was examined. Eleven mild to moderate hypertensives (supine diastolic pressures from 95 to 105 mmHg), experienced in the consistent performance of the Valsalva maneuvre, had their previous medications withdrawn over a period of one week and were then administered placebo twice daily for the next four weeks. At the end of this period, and 3 h after the last dose of placebo, each patient had a retrograde catheter inserted into an antecubital vein followed by a 30 min rest period in the supine position. Blood was sampled for resting catecholamine determination, followed by measurement of resting systolic and diastolic blood pressures together with forearm bloodflow. Each patient then performed the Valsalva maneuvre (40 mmHg, 40 s) with continuous recording of heart rate. Forearm bloodflow was again recorded after 25 s of straining while blood was sampled at the point of bradycardia after straining. During a duplicate Valsalva maneuvre, systolic and diastolic blood pressures were recorded after 30 s of straining. All patients exhibited the appropriate heart rate responses to the Valsalva maneuvre (resting 76 +/- 15 beats/min; tachycardia 101 +/- 13, P less than 0.001; bradycardia 65 +/- 18, P less than 0.01). Forearm bloodflow was reduced (P less than 0.001) during the maneuvre while mean arterial pressure (P less than 0.001), forearm vascular resistance (P less than 0.001), plasma noradrenaline (P less than 0.001) and adrenaline (P less than 0.05) levels were all increased.(ABSTRACT TRUNCATED AT 250 WORDS)

The 24 h blood pressure responses of hypertensives to a once-a-day cilazapril regimen.

The efficacy of once-a-day cilazapril (a new long acting converting enzyme inhibitor) therapy for the 24 h control of hypertension and its effects on the renin-angiotensin axis were investigated. Twenty-four uncomplicated hypertensive patients whose sitting diastolic blood pressures remained within 94 to 114 mmHg after four weeks of placebo were randomly assigned on a double-blind basis to receive either continued placebo or cilazapril therapy at a single dose of 1.25, 2.5 or 5.0 mg/day for a further four weeks. At the end of weeks 4 and 8, systolic and diastolic blood pressures and heart rates were recorded, supine and standing, at 0, 2, 4, 6, 9, 12 and 24 h following a single dose of drug. At the same times, blood was withdrawn for determination of plasma renin activity and aldosterone. Supine and erect systolic and diastolic blood pressures were lowered to normotensive levels with an optimal response being achieved at a dose of 2.5 mg/day. Supine and erect heart rates were unchanged with respect to drug dosage, and the reflex increase in heart rate and diastolic blood pressure on changing from supine to erect posture was maintained in all groups. Maximum antihypertensive efficacy was from 2 to 6 h after drug ingestion. There were no changes in resting aldosterone, but plasma renin activity was increased at all drug dosages. A single 2.5 mg dose of cilazapril provides blood pressure control for a 24 h period. Cilazapril does not appear to interfere with the reflex autonomic responses to postural change.

Bevantolol attenuates thiazide stimulated renin secretion and catecholamine release in diuretic resistant hypertensives.

An attempt was made to establish whether cardioselective beta-blockade could counteract the stimulation by hydrochlorothiazide of the renin-angiotensin and sympathetic nervous systems and to what extent such actions contributed to the antihypertensive effect of bevantolol. The hemodynamic and neurohumoral responses of 21 thiazide resistant hypertensives who had received sequential chronic therapy with hydrochlorothiazide, hydrochlorothiazide combined with bevantolol and bevantolol monotherapy were compared. In these patients, bevantolol had a negative chronotropic effect and appeared, when administered alone, to induce an overall lowering of sympathetic nervous system activity without inhibiting the reflex responses of peripheral vascular resistance to postural change or lowered heart rate. When bevantolol and hydrochlorothiazide were administered together, sympathetic activity appeared to be maintained, possibly as a reflex response to volume depletion but vascular resistance did not appear to be responsive to baroreceptor stimulation. Diminished vascular reactivity induced by the hydrochlorothiazide is suspected to be a contributory factor. Inhibition of thiazide stimulated renin release by bevantolol may contribute to the antihypertensive effect of the combined therapy.

Hemodynamic and adrenergic responses of bevantolol and propranolol in hypertensives.

The hemodynamic and neurohumoral responses of 21 thiazide-resistant hypertensives receiving sequential chronic therapy with propranolol and bevantolol, a new cardioselective beta-1 blocker, were studied and compared with their responses to placebo. The objective was to determine to what extent decreased circulation levels of catecholamines and renin activity contributed to the hypotensive action of bevantolol and whether it demonstrated a significant sparing effect on vascular resistance. Both propranolol and bevantolol lowered supine and erect blood pressures to a comparable extent but the response of diastolic pressure to upright posture was maintained. Resting heart rates were lowered and postural tachycardia was attenuated. Propranolol induced a greater decrease in forearm blood flow and greater increase in vascular resistance than bevantolol. Both drug therapies were associated with lowered plasma concentrations of noradrenaline and adrenaline, while the decrease in noradrenaline levels was linearly related to the fall of mean arterial pressure for both drugs. Plasma renin activity was lowered only to a marginal extent by either drug but aldosterone concentrations were significantly reduced to a comparable extent by both drugs. The results suggest that a negative chronotropic action on the heart and an overall reduction in sympathetic nervous tone both contribute to the hypotensive effects of bevantolol and propranolol, but reduction of plasma renin activity may be of lesser importance. Bevantolol demonstrated a significant vascular sparing effect in this patient group compared with propranolol.

Cilazapril inhibits vascular responses to baroreflex-stimulated sympathetic neural activity in hypertensive patients.

The responses of forearm bloodflow and heart rate to the Valsalva maneuvre were investigated in patients treated with placebo or cilazapril, a new angiotensin converting enzyme inhibitor. Twenty-four uncomplicated hypertensives, whose sitting diastolic blood pressures remained within 94 to 114 mmHg after four weeks of placebo therapy, were randomly assigned on a double-blind basis to receive either further placebo or cilazapril (1.25 to 5.0 mg/day, single dose) for a further four weeks. At the end of weeks 4 and 8, each patient performed standardized Valsalva maneuvres before and 2 h after the day's dose of medication. For each maneuvre, forearm bloodflow was measured in the resting phase and at the point of maximum tachycardia during the straining phase, together with a continuous record of heart rate. All patients exhibited the appropriate heart rate response to the maneuvre with marked tachycardia followed by bradycardia on release of straining. There were no differences in the degree of tachycardia, bradycardia or the Valsalva ratio as a result of cilazapril therapy. There were no changes in resting forearm bloodflow as a result of drug therapy but the flow was reduced (P less than 0.01) during the straining period of all maneuvres. The relative decrease in flow during the maneuvre was attenuated (P less than 0.05) in the cilazapril-treated patients at all drug doses but not in those taking placebo. Cilazapril appears to inhibit the sympathetic nervous system response to the baroreceptor stimulation of the Valsalva maneuvre but not the parasympathetic response of heart rate.

Higher plasma Na+,K+-ATPase inhibitory activity in essential hypertensive patients.

The ability of plasma to inhibit 86 rubidium uptake in rat aorta and to displace [3H]-ouabain from hog brain Na+,K+-ATPase was used as a measure of plasma Na+,K+-ATPase inhibitory activity in seven normotensive and eight hypertensive subjects. Rat aortae rings were incubated in oxygenated plasma containing 86 rubidium (2 microCi/mL) for 30 mins at 37 degrees C and uptake measured and expressed as mumol/kg wet weight/min. Plasma was extracted with a mixture of chloroform and methanol (2:1) and the extract separated by silicic acid column followed by thin layer chromatography and fractions assayed for ouabain displacement using digoxin as a standard. Total ouabain displacement was calculated as the sum of all fractions. There was a strong correlation between the two methods for total plasma Na+,K+-ATPase inhibitory activity (r = 0.761, P less than 0.01). There was a significant positive correlation between plasma Na+,K+-ATPase inhibitory activity and blood pressure in all subjects. Na+,K+-ATPase inhibitory activity was significantly higher in plasma of hypertensives by both methods (P less than 0.001). The increased Na+,K+-ATPase inhibitory activity in plasma from hypertensives was due to the nonesterified fatty acid, long chain acylcarnitine and diphosphatidylglycerol fractions.

Can plasma catecholamine levels be a useful index of sympathetic nervous system activity?

The hemodynamic responses of the sympathetic nervous system to the Valsalva maneuver were related to changes in circulating levels of catecholamines, aldosterone and plasma renin activity. Fourteen healthy normotensives (aged 27 +/- 8 years) took part. A catheter was inserted in the forearm then the subject was rested quietly (supine) for 30 mins. The Valsalva maneuver was performed (duration 40 s, intrathoracic pressure 40 mmHg) with continuous recording of supine heart rate. Blood was sampled before the maneuver (basal state) and at the bradycardic post maneuver phase for measurement of plasma noradrenaline, adrenaline, renin activity and aldosterone. In six subjects the procedure was repeated for durations of 10, 20, 30 and 40 s with a 30-min rest between each maneuver. Plasma catecholamines increased consistently (P less than 0.001) from pre- to post bradycardic phases of the maneuver. No changes in plasma renin activity or aldosterone were observed. The maximum tachycardia observed during each maneuver and the increments in catecholamine concentrations were each linearly related to the duration of straining but there was no overall correlation between the tachycardia and catecholamine concentrations. In conclusion under controlled conditions, plasma catecholamine concentrations can be useful indices of the stimulation of the sympathetic nervous system; the Valsalva maneuver does not appear to affect significantly the peripheral renin-angiotensin system; and the heart rate response to the Valsalva maneuver does not appear to be mediated solely by the sympathetic nervous system.

Correlation of left ventricular hypertrophy and its regression by lisinopril with salt-induced hypertension.

The interaction of salt with hypertension-induced left ventricular hypertrophy and its reversal by inhibition of angiotensin converting enzyme were studied in salt sensitive and salt resistant Dahl rats. Eight-week-old rats were fed either a low or high salt diet for three weeks. The colonies were then further divided and either treated with lisinopril or given no treatment for 11 weeks. Untreated salt sensitive rats had higher blood pressures than salt resistant animals. Left ventricular weight and wall thickness in both untreated salt sensitive groups was higher than in the resistant groups. Therapy lowered blood pressures in all groups but those of the high salt group remained higher than the low salt group. Reduction of left ventricular weight and wall thickness took place in either strain only when salt intake was low. Right ventricular and atrial weights were largely unaffected either by salt intake or drug therapy. Plasma renin activity increased and aldosterone levels decreased with lisinopril therapy in all groups except the salt sensitive, high salt group where both remained unchanged at low levels. Lisinopril was effective in reducing blood pressure and left ventricular hypertrophy, but both effects were severely impaired by high salt intake. The major determinant of left ventricular hypertrophy appeared to be afterload, as shown by a good correlation between left ventricular mass and systolic blood pressure, but there was some indication of a possible independent hypertrophic action of salt.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac hypertrophy in experimental hypertension: interaction of the sodium ion, blood pressure and lisinopril.

The interaction of blood pressure, salt intake and the inhibition of angiotensin converting enzyme activity with cardiac hypertrophy were examined in the Dahl rat model. Eight-week-old salt sensitive and salt resistant rats were each separated into two colonies, one of which was maintained on a low salt and the other on a high salt diet for three weeks, at the end of which time both salt sensitive colonies were hypertensive. Each colony was then separated into two groups, one received no medication the other was given lisinopril until normotension was achieved. After 11 weeks of therapy, intra-arterial blood pressures and heart rates were recorded. The rats were sacrificed and heart weight to body weight ratios were determined. Both untreated salt sensitive groups displayed marked cardiac hypertrophy which correlated well with diastolic blood pressure irrespective of salt intake. Lisinopril therapy lowered blood pressures to normotensive levels in all groups except for salt sensitive rats ingesting a high salt diet where, despite a 10-fold increase in drug dose, normotension was not achieved. Significant cardiac regression accompanied lisinopril therapy in rats receiving low salt diets but high salt intake severely attenuated regression in both strains. There was no significant correlation between heart weight and blood pressure in the treated groups. The results suggest that cardiac regression appears to be mediated by other factors besides ventricular afterload pressure and that high salt intake adversely affects blood pressure and heart weight response to lisinopril therapy.

Pharmacological abnormality of kallikrein-kinin system in hypertension.

Until recently the possible role of vasodilator systems in the etiology of hypertension has been largely ignored, although deficiency of vasodilator influence could be more important than the presence of vasoconstriction in determining vascular tone. Lower concentrations of urinary kallikrein excretion have been widely indicated in clinical and in several experimental hypertensive situations. The reduced plasma kininogen levels may reflect either decreased synthesis compensating for a chronically reduced kinin generation or genetic abnormality leading to reduced plasma kininogen, which may be a predisposing factor in hypertension. An alternative possibly could be enhanced adrenergic control during hypertensive conditions which may cause reduction in prostaglandin and kallikrein-kinin systems. It has also been suggested that most of the pharmacological actions of the kallikrein-kinin system are mediated through prostaglandin formation. Thus, subnormal kallikrein-kininogen-kinin concentrations could be the cause of reduced vasodilating influence leading to both clinical and experimental hypertension.