Discussion on the natriuretic effect of calcium antagonists.
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Animals↗
Biomedical subjects
A Zanchetti
Publications and source records attributed to A Zanchetti.
Antihypertensive effect of a new formulation of slow release oxprenolol in essential hypertension.
To test whether a new formulation of a slow release oxprenolol (SLOx) can produce a steady 24-h antihypertensive effect, we recorded 24-h intraarterial blood pressure (Oxford technique) in eight ambulant inpatients (age 44.5 +/- 3.0 years, mean +/- SE) with a mild or moderate hypertension who were untreated since three weeks. The study was started seven days after hospitalization and was conducted according to a randomized doubleblind cross-over design. Blood pressure recordings were made after (a) a 7-day administration of SLOx in a single evening dose, and (b) a 7-day administration of placebo. This design allowed to determine the effect of SLOx without interference from nonspecific blood pressure lowering factors. Blood pressure effects of handgrip, submaximal cyclette exercise, and cold pressor test 20-24 h after the administration of SLOx and placebo were also evaluated. The blood pressure tracing was analyzed beat-to-beat by a computer which provided also the analysis of the heart rate data. The 24-h mean systolic and diastolic blood pressure measured during placebo were 144.6 +/- 6.4 and 81.1 +/- 3.9 mm Hg, the corresponding heart rate being 76.9 +/- 3.5 beats/min. SLOx reduced these values by 6.2, 10.6, and 4.8%, respectively, all effects being similarly evident throughout the blood pressure recording. The pressor responses to handgrip, cyclette exercise, and cold pressor test were not affected by SLOx. By contrast, the small tachycardic response to handgrip and the large tachycardic response to submaximal cyclette exercise were significantly reduced by the drug.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Vasodilatation in hypertension: the relevance of ISA. Concluding paper.
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Adrenergic beta-Antagonists↗
Renal reflexes in the regulation of blood pressure and sodium excretion.
The rich innervation of the kidney is distributed to all structures of renal parenchyma thus providing important anatomical support to the functional evidence that the renal nerves can control kidney functions and send signals on the kidney environment to the central nervous system. Efferent renal nerve fibres are known to influence renal haemodynamics by modifying arteriolar vascular tone, renin release by a direct action on juxtaglomerular cells, and the excretion of sodium and water by changing tubular reabsorption of sodium and water at the different tubular levels. Mechano- and chemo-receptors have been shown in the kidney. Afferent fibres connected with renal receptors convey signals to the central nervous system both at spinal and supraspinal levels. The central areas receiving inputs from the kidney are those involved in the control of cardiovascular homeostasis and fluid balance. Activation of renal receptors by the electrical stimulation of renal afferent fibres were found to elicit both excitatory and inhibitory sympathetic responses. Although the existence of excitatory renorenal reflexes has been suggested, electrophysiological and functional data demonstrate that neural renorenal reflexes exert a tonic inhibitory influence on the tubular sodium and water reabsorption and on the secretion of renin from the juxtaglomerular cells.
Afferent Pathways↗
Neural, hemodynamic, and renal responses to stimulation of intestinal receptors.
Stimulation of visceral receptors with bradykinin has been shown to cause reflex increases in sympathetic nerve activity and systemic arterial pressure. In this investigation, serosal receptors of the intestine were stimulated by bradykinin in anesthetized cats to 1) compare mesenteric and renal sympathetic responses, 2) compare hemodynamic responses in mesenteric and renal beds, and 3) determine changes in renal function. This stimulation in intact animals caused pressor responses, significantly greater excitation of mesenteric than renal nerves, significantly greater mesenteric than renal vasoconstriction, diuresis, natriuresis, and, in denervated kidneys, increases in fractional sodium excretion. In vagotomized, sinoaortic-denervated cats, stimulation of intestinal receptors caused excitation of mesenteric nerve activity greater than renal for only 30 s. This sympathetic reflex response led to pressor responses, equal mesenteric and renal vasoconstriction, diuresis, natriuresis, and increased fractional excretion of sodium only in denervated kidneys. When abdominal perfusion pressure was held constant with an aortic snare in these same animals, the sympathetic reflexes initially caused greater mesenteric than renal vasoconstriction and antidiuresis and antinatriuresis only in innervated kidneys. These findings demonstrate that the intensity of hemodynamic and renal responses to stimulation of visceral receptors correlates well with the magnitude of sympathetic nerve responses.
Animals↗
Alerting reaction and rise in blood pressure during measurement by physician and nurse.
Blood pressure was monitored by a continuous intra-arterial recording in 46 subjects to investigate whether the alarm reaction and the blood pressure and heart rate increases that occur during cuff blood pressure measurement made by a physician 1) attenuate when the physician's visit is repeated several times and 2) are less pronounced if a nurse measures the blood pressure. In 16 subjects the peak mean blood pressure and heart rate rises that occurred in the early part of the physician's first visit (22.6 +/- 1.8 mm Hg and 17.7 +/- 1.7 beats/min) were virtually identical to those occurring during three subsequent visits by the same physician throughout a 2-day intra-arterial blood pressure monitoring. The less pronounced pressor and tachycardic responses observed in the last part of the physician's visit also were virtually identical among the four visits. In contrast, in 30 other subjects the blood pressure and heart rate rises that occurred during the nurse's visit were 46.7% and 42.1% less (p less than 0.01) than those occurring during the physician's visit. The late and less pronounced pressor and tachycardic responses to the visit were also significantly less (p less than 0.01) in the former than in the latter condition. These results indicate that the error of overestimation of blood pressure inherent in cuff blood pressure measurement by a physician cannot be avoided by repeated visits by the physician over a short time span. It clearly can be reduced, however, if blood pressure measurements are performed by a nurse.
Emotions↗
Renal effects of felodipine in hypertension.
The results of 2 recent studies on the renal effects of felodipine in hypertensive patients are described. Antihypertensive doses of felodipine (10mg bid) displayed a clear natriuretic and diuretic effect associated with a constant glomerular filtration rate and an increase in renal plasma flow. With higher doses of felodipine (up to 50mg tid), the natriuretic effect was reversed to an antinatriuretic effect, accompanied by a reduction in glomerular filtration rate. The natriuretic effect of felodipine 10mg bid was evident during the first 2 days of administration, but a negative sodium balance was still present at the end of the seventh day. The mechanisms of the renal effects of calcium antagonists are discussed as well as the relevance of the natriuretic effect for the antihypertensive action of these compounds.
Antihypertensive Agents↗
Comparative measurements of immunoreactive renin, plasma renin activity and angiotensin II in human plasma.
In human plasma samples we compared the values of renin activity, determined with a conventional enzymatic assay, with those of immunoreactive renin, determined with a new, direct immunoradiometric assay which employs highly specific monoclonal antibodies, and with those of angiotensin II; the comparative measurements of renin were carried out also in trypsin activated samples of nephric and anephric subjects. We found that, overall, there was a close relationship between renin activity and immunoreactive renin; however, this relationship was absent when the statistical analysis was restricted to plasmas with low or very low renin. We also found that, within a rather wide range of values, angiotensin II was more closely correlated with immunoreactive renin than with renin activity. Trypsin activation increased to a similar extent immunoreactive renin and renin activity in plasma of nephric and anephric subjects and, overall, the values of total renin obtained with the two assays were significantly correlated. The results of these comparative determinations indicate that, in general, the measurement of immunoreactive renin represents a valid alternative to that of renin activity and a reliable index of the activity of the renin-angiotensin system. In addition, studies with trypsin activation suggest that even in the anephric state human plasma contains an inactive enzyme convertible into an active form which has immunological properties similar to those of active renin.
Angiotensin II↗
Evaluation of a new non-invasive semiautomatic blood pressure monitoring device.
The accuracy of a new device for indirect blood pressure measurement was evaluated by comparison with the intra-arterial pressure measurement. The device is based on the Korotkoff's method using a cuff and a microphone, but is characterized by a two-channel recorder to monitor the cuff pressure and the events picked up by the microphone. The blood pressure is determined automatically by a computer program which analyzes the microphone signal during a cuff deflation, and manually by the same criteria to confirm the result. The comparison was carried out on 29 subjects undergoing catheterization of the brachial artery for clinical examination. The difference between the direct and indirect reading ranged from -14 to +9 mmHg (-0.55 +/- 0.91, mean +/- SE) for the systolic pressure and from -5 to +14 mmHg (3.78 +/- 0.95) for the diastolic pressure. It was found advantageous that blood-pressure reading can be confirmed repeatedly on the recorded chart after the measurement.
Adult↗
Cardiovascular effects of afferent renal nerve stimulation.
Electrical stimulation of afferent renal nerves elicits an increase in arterial pressure and heart rate. The hypertensive response is presumably due to the widespread activation of the sympathetic nervous system leading to peripheral vasoconstriction. Interestingly, the kidney does not appear involved in this reflex excitatory response to afferent renal nerve stimulation since changes in vascular conductances and excretory functions are equal in both the innervated and denervated kidney, and secondary to changes in renal perfusion pressure. In addition, no changes in renin release from either kidneys are observed during afferent renal nerve stimulation. It is likely that the electrical stimulation of afferent renal nerves activates other reflexes exerting an inhibitory influence on efferent renal nerve activity. Indeed, neural renorenal reflexes which tonically inhibit renal functions have clearly been demonstrated. Furthermore, preferential inhibition of efferent renal nerve activity by cardiopulmonary and sinoaortic receptors has recently been shown during activation of other visceral afferents.
Afferent Pathways↗
Resting and postexercise hemodynamic effects of carvedilol, a beta-adrenergic blocker and precapillary vasodilator in hypertensive patients.
Carvedilol is a recently developed antihypertensive drug that combines in the same molecule a nonselective beta-adrenoceptor blocking effect and a vasodilating precapillary activity. In our study, we have investigated the effects of carvedilol 25 mg b.i.d. on blood pressure, heart rate, and plasma noradrenaline in hypertensive patients at rest and during exercise after acute and repeated oral administration for 7 days. The daily average supine blood pressure of the 12 patients with essential hypertension was 178 +/- 10/107 +/- 3 mm Hg (means +/- SD of 8 measurements in each patient) after placebo and was significantly (p less than 0.01) reduced to 162 +/- 17/99 +/- 8 mm Hg on the first day and to 158 +/- 15/96 +/- 8 mm Hg on the seventh day of carvedilol treatment. Similar values were found in the upright posture. Heart rate was slightly but significantly lowered during acute and repeated administration. The exercise-induced increase in systolic blood pressure was significantly reduced by carvedilol 25 mg b.i.d., while there was a nonsignificant reduction in the tachycardic response. There was a significantly greater rise in plasma noradrenaline during exercise on the seventh day of carvedilol treatment. Carvedilol significantly lowered blood pressure and heart rate at rest and the exercise-induced rise in systolic blood pressure.
Administration, Oral↗
Hemodynamic effects of acute and prolonged administration of nitrendipine in essential hypertension.
In six hospitalized subjects with mild or moderate and untreated essential hypertension, we measured mean blood pressure (MBP, brachial artery catheter), heart rate (HR, electrocardiogram), cardiac output (CO, thermodilution), and total peripheral resistance (TPR, MBP divided by CO) at rest and during a cold pressor test (CPT, 60 s), a hand-grip exercise (HG, 40% maximum strength for 90 s), and a cyclette exercise (CE, 50 W for 5 min). The study was performed in a no-drug condition, 1 h after 20 mg oral nitrendipine (aN) and 1 week after daily administration of 20 mg oral nitrendipine (pN). Compared with the no-drug condition, aN reduced resting MBP from 137.3 +/- 7.3 (mean +/- SEM) to 112.3 +/- 9 mm Hg (p less than 0.05), increased resting HR from 72.3 +/- 6.9 to 85.3 +/- 8.8 beats/min) (p less than 0.05), increased resting CO from 6,191 +/- 508, to 8,700 +/- 1,050 ml/min (p less than 0.05), and reduced resting TPR from 1,807 +/- 119 to 1,140 +/- 228 dynes/s/cm5 (p less than 0.05). The reduction in resting MBP and TPR were unchanged by pN, whereas the increase in HR and CO were attenuated by 47 and 42%, respectively (p less than 0.05). Neither aN nor pN altered the hemodynamic responses to CPT, HG, and CE. As a result, the peak MBP and TPR values that were measured during these maneuvers were always lower (p less than 0.05) during aN and pN than in the no-drug condition. Thus, nitrendipine exerts marked antihypertensive and vasodilatatory effects that are evident at rest and during conditions elevating BP.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Effects of different sodium intakes on the antihypertensive and renal effects of single oral doses of nifedipine in hypertensive patients.
The aim of this study was to investigate whether the antihypertensive and renal effects of Ca2+ antagonists are related to the sodium state of the patients. For this purpose, in a group of 11 patients with essential hypertension we have compared the blood pressure lowering effects of a single oral dose of nifedipine before (100 mmol Na+/day and 40 mmol K+/day) and after sodium depletion (20 mmol Na+/day and 40 mmol K+/day: each period was of 6-8 day duration). During the normal sodium diet nifedipine significantly lowered supine blood pressure (from 185 +/- 13/107 +/- 7 to 161 +/- 13/100 +/- 7 mm Hg, p less than 0.001) and induced a significant rise in Na+ excretion (from 52 +/- 10 to 94 +/- 13 mmol/6 h) and in urine volume (from 520 +/- 80 to 947 +/- 120 ml/6 h; p less than 0.01). Sodium depletion significantly lowered supine blood pressure (152 +/- 12/95 +/- 9 mm Hg, p less than 0.001); nifedipine caused a further and significant blood pressure reduction (142 +/- 11/90 +/- 8 mm Hg, p less than 0.01), but only a minor and not significant increase in sodium excretion (from 10 +/- 2 to 22 +/- 5 mmol/6 h) and urine volume (from 338 +/- 76 to 463 +/- 94 ml/6 h). Our data suggest that the natriuretic action of calcium antagonists is not relevant to their antihypertensive effect.
Administration, Oral↗
Evaluation of the antihypertensive effect of TTS clonidine by multiple 24-hour automatic blood pressure monitoring.
Transdermal clonidine (TTSC) has been proposed as a means to improve compliance to treatment of hypertensive patients because of the reported 7-day duration of its antihypertensive effect. However, no detailed information is available on the onset, the time course, and the day and night distribution of this effect throughout the 7 days of the drug skin application. In 12 hospital in-patients with mild or moderate untreated essential hypertension, 24-h blood pressure (BP) was measured at 10-20 min intervals via a noninvasive automatic device (Spacelabs 5300 M) in a no-drug condition, on the 2nd, 4th, and 7th day of the arm application of a 7.0 or 10.5 cm2 patch of TTS clonidine, and on the 2nd and 4th day after substitution of the TTS clonidine patch with an identical patch containing an inert substance (placebo). In nine out of 12 patients, TTS clonidine reduced 24-h systolic and diastolic blood pressure at the 2nd day and even more so on the 4th and 7th day of its application. The reduced blood pressure values observed on the 7th day increased progressively on the 2nd and 4th day after TTS clonidine removal with no rebound over the pre-drug values. The hypotensive effects observed during TTS clonidine were evident throughout the day and night. Thus TTS clonidine exerts a hypotensive effect that starts early and is maintained throughout the 7 days and nights of its application. The discontinuation of this treatment is associated with a smooth return of blood pressure values towards the pre-treatment levels.
Administration, Cutaneous↗
Blood pressure and organ damage.
Casual blood pressure measurements can predict the development of cardiovascular morbidity and mortality, but especially in mild hypertension the correlation indices between casual measurements of blood pressure and the subsequent occurrence of complications are low. Casual and office blood pressure measurements, however, provide a very limited and biased assessment of blood pressure as a risk factor since blood pressure is known to change from moment to moment and to be influenced by its very measurement. Considerable advances in our understanding of the factors influencing blood pressure during daily life and in assessing blood pressure variability have been made possible by use of portable equipment for continuous intraarterial recording of blood pressure. Equipment for noninvasive ambulatory blood pressure monitoring is also available; this equipment is more practical than intraarterial equipment, but is associated with some degree of error and several limitations. Data are reported from a recent study conducted by our group in which target organ damage in 108 hypertensive patients was correlated with blood pressure values as measured by a cuff sphygmomanometer and with various indices derived from 24-h intraarterial blood pressure monitoring. The findings indicate that the incidence and severity of organ damage are more closely related to 24-h blood pressure means than to cuff values. They also provide the first unequivocal evidence that target organ damage also relates to blood pressure variability.
Behavior↗
Converting-enzyme inhibition and coronary blood flow.
The effects of converting-enzyme inhibition (25 mg oral captopril) on coronary hemodynamics in the presence and absence of activation of the renin-angiotension system were studied in 10 patients with mild essential hypertension with no evidence of ischemic heart disease. Coronary blood flow was determined by thermodilution before and after 1 week of diuretic therapy in six patients and before and after placebo in four patients. The diuretic (50 mg/day furosemide) reduced coronary blood flow and increased coronary vascular resistance; in these same patients, captopril reduced mean arterial pressure and the rate-pressure product but increased coronary flow significantly. There was no change in any of these variables after captopril in the placebo group. Similar results were obtained in normotensive rats treated with hydrochlorothiazide; the increase in coronary flow after captopril correlated significantly with the control plasma renin activity. These results in hypertensive humans and normotensive experimental animals indicate that diuretic therapy reduces coronary blood flow significantly, and angiotensin can play a significant role in modulating coronary vascular resistance under conditions associated with activation of the renin-angiotensin system.
Adult↗
Control of renal renin release.
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Angiotensin II↗
Effectiveness of Sepharose-bound trypsin versus liquid-phase trypsin plus benzamidine for activation of inactive renin in human plasma.
We compared the effectiveness of two techniques involving the use of the enzyme trypsin to activate inactive renin in human plasma. Both these methods were developed to optimize activation with trypsin by preventing the possible destruction of activated renin by trypsin itself. In one method, an antitryptic agent such as benzamidine is added to plasma, concomitantly with trypsin (liquid phase). In the other a low concentration of Sepharose-bound (immobilized) trypsin is used. In six plasma samples we have found that trypsin (1.5 mg/ml) activation, with or without benzamidine (0.8 mg/ml), yielded similar values of activated renin (11.0 +/- 2.7 vs. 11.3 +/- 2.3 ng/ml/hr). However, the addition of immobilized trypsin to pool plasma pretreated with trypsin plus benzamidine caused a further increase in plasma renin activity (PRA); in contrast, the addition of trypsin and benzamidine to pool plasma pretreated with immobilized trypsin caused a decrease in PRA. In 17 plasma samples from patients with essential hypertension we found that the inactive renin values were always higher after treatment with immobilized trypsin than with trypsin plus benzamidine (9.0 +/- 0.7 vs. 6.1 +/- 0.5 ng/ml/hr, P less than 0.01); moreover, there was a positive correlation between the differences in the values of inactive renin measured with the two methods and the values obtained with immobilized trypsin (r = 0.64, P less than 0.01). Therefore, the activation with immobilized trypsin is more effective than that with liquid-phase trypsin, alone or in combination with benzamidine, in converting inactive renin in human plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
Amidines↗