Maria Luisa Stella

Heart rate as marker of sympathetic activity.

Objective To determine the value of the supine heart rate as a marker of sympathetic tone by assessing, in a large group of subjects, the relationships between this parameter and two other indices of sympathetic activity, plasma norepinephrine and sympathetic nerve traffic. Patients and methods We studied 243 subjects aged 50.0 ± 12.1 years (mean ± SD). Of these, 38 were normotensive healthy controls, 113 subjects had untreated essential hypertension, 27 were obese normotensives and 65 had congestive heart failure. In each subject, over a 10 min supine period, we measured mean arterial pressure (Finapres), heart rate (electrocardiogram), venous plasma norepinephrine (high-performance liquid chromatography) and efferent postganglionic muscle sympathetic nerve activity (microneurography at a peroneal nerve). Results In the whole study group, supine heart rate was correlated with both plasma norepinephrine (r = 0.32, P < 0.0001) and muscle sympathetic nerve activity (r = 0.38, P < 0.0001). This was also the case in the normotensive obese subjects and the heart failure subjects considered separately. Heart rate values were greater in the obese and the heart failure patients than in controls (75.1 ± 13.0 and 78.2 ± 13.0 versus 69.2 ± 11.6 beats/min; P < 0.05 and P < 0.001, respectively), as were plasma norepinephrine (362.7 ± 202 and 400.3 ± 217 versus 230.4 ± 126 pg/ml; P < 0.01 and P < 0.001, respectively) and muscle sympathetic nerve activity (44.1 ± 14.7 and 55.3 ± 14.3 versus 27.8 ± 11.0 bursts/min; P < 0.001 for both). In contrast, in the essential hypertensive subjects, no significant relationship was found between these three indices of sympathetic activity. Furthermore, in the hypertensives, the heart rate was not increased, at variance with the sympathetic nerve traffic, which was greater than in controls (36.2 ± 10.0 versus 27.8 ± 11.0 bursts/min, P < 0.001). Conclusions These data suggest that the supine heart rate can be regarded as a marker of intersubject differences in sympathetic tone, and that this is the case both in the general population and in those with cardiovascular diseases. Its value for this purpose is limited, however, and the limitations may be more evident in essential hypertension than in conditions such as obesity and heart failure.

Impaired radial artery compliance in normotensive subjects with familial hypercholesterolemia

Hypercholesterolemia impairs arteriolar dilatation, but whether the vascular abnormalities accompanying this condition include large artery function is unknown. We addressed this issue in 13 normotensive subjects with familial hypercholesterolemia (serum cholesterol 401.6 +/- 16.9 mg/dl, mean +/- S.E., FHC) and no evidence of atherosclerotic lesions, in whom radial artery (RA) diameter and blood pressure (BP) were measured beat to beat by an echotracking and a Finapres device, respectively. RA compliance (RAC) was derived from the diameter/BP relationship and expressed over the systo-diastolic BP range, both at baseline and after a 12-min brachial artery occlusion. RAC was expressed also as the area under the RAC/BP curve divided for pulse BP. Measurements included maximal forearm blood flow (plethysmography) and minimal forearm vascular resistance (FVR) which were obtained from the values following the 12-min brachial arterial occlusion. Data were collected before and after 6- and 24-month lipid lowering treatment (simvastatin 40 mg/day). Ten age-matched normotensive normocholesterolemic healthy subjects (N) served as controls. Compared to N, baseline RAC was strikingly reduced in FHC (-53.5%, P < 0.01). After ischemia RAC increased significantly and markedly in N (+38.7, P < 0.01), while only a modest and non-significant increase was observed in FHC. Minimal FVR was markedly higher in FHC than in N (3.5 +/- 0.9 vs 1.6 +/- 0.1 units, P < 0.01). In FHC (7 subjects) RAC remained unchanged after 6 months of lipid lowering treatment, but increased markedly (+55.2%, p < 0.05) when treatment was prolonged to 24 months. Lipid lowering treatment also reduced minimal FVR, the effect being significant both after 6 and after 24 months. No changes in RAC and minimal FVR were seen after 6 months in controls. Thus, in subjects with a marked increase in serum cholesterol due to FHC, not only arteriolar dilatation, but also RAC and distensibility are markedly impaired. This impairment can be favourably affected by an effective lipid lowering treatment of long duration.

Acute effects of smoking on radial artery compliance in humans.

Objective To clarify whether the acute and marked increase in blood pressure associated with smoking is accompanied by an alteration in arterial compliance. Design Arterial compliance was measured in 13 subjects before and after smoking a cigarette with a nicotine content of 1.2mg, or before and after sham smoking. Measurements were obtained with the subjects at rest and after prolonged brachial artery occlusion (12min). Methods Compliance was measured using an echo-tracking system capable of continuously providing (300 readings/s) radial diameter data and, with the addition of a photoplesythmographic device, blood pressure measurement. Results Acute cigarette smoking caused a pressor and tachycardie response, and decreased markedly both resting radial artery diameter and compliance, at blood pressure values identical to those before smoking. The marked increase in radial artery diameter and compliance brought about by local ischaemia was unaffected by smoking, and no changes were observed both at rest and after ischaemia as a result of sham smoking. Conclusions Smoking causes a marked reduction in radial artery compliance, and the effect is independent of the increase in blood pressure. However, the marked increase in compliance due to ischaemia is not modified by smoking.

Effect of chronic angiotensin converting enzyme inhibition on sympathetic nerve traffic and baroreflex control of the circulation in essential hypertension.

Background Human studies have shown that the blood pressure lowering effects of angiotensin converting enzyme inhibitors are accompanied by a reduction in plasma norepinephrine levels. Whether this is due to central or peripheral mechanisms is unknown, however. Objective To evaluate the effects of chronic interference with the renin–angiotensin system on sympathetic nerve traffic and baroreflex control of vagal and adrenergic cardiovascular drive. Patients and methods In 18 untreated mild to moderate essential hypertensive patients aged 48.5 ± 1.9 years (mean ± SEM), we measured mean arterial pressure (Finapres), heart rate (electrocardiogram), plasma renin activity (radioimmunoassay), plasma norepinephrine (high-performance liquid chromatography) and postganglionic muscle sympathetic nerve activity (microneurography at a peroneal nerve). In nine patients, measurements were performed before and after 2 months of oral administration of lisinopril (10 mg/day), while in the remaining nine patients they were performed before and after a 2 month observation period, without the drug administration. Measurements were performed at rest and during baroreflex stimulation and deactivation elicited by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Results Lisinopril induced a marked increase in plasma renin activity (from 1.1 ± 0.2 to 6.4 ± 1.3 ng/ml per h, P < 0.01) and a reduction in mean arterial pressure (from 109.6 ± 3.1 to 98.7 ± 2.9 mmHg, P < 0.01) without affecting the heart rate. Plasma norepinephrine and muscle sympathetic nerve activity values were not significantly different before and after lisinopril treatment (plasma norepinephrine values changed from 290.4 ± 39.2 to 308.1 ± 67.1 pg/ml; muscle sympathetic nerve activity changed from 56.4 ± 5.3 to 50.6 ± 6.6 bursts/100 heart beats). Neither the sympathoinhibitory nor the sympathoexcitatory responses to phenylephrine and nitroprusside were affected by lisinopril, nor the concomitant bradycardia and tachycardia. The curves relating mean arterial pressure to heart rate and muscle sympathetic nerve activity values during baroreceptor manipulation were shifted to the left, indicating a resetting of the baroreflex to the lower blood pressure values achieved during treatment. Conclusions In essential hypertension, sympathetic nerve traffic is not affected by chronic angiotensin converting enzyme inhibitor treatment that effectively interferes with the renin–angiotensin system and lowers the elevated blood pressure. The baroreflex ability to modulate heart rate and central sympathetic outflow is also unaffected. These data argue against the existence of a central sympathoexcitatory effect of angiotensin II in this condition. They also indicate that antihypertensive treatment with an angiotensin converting enzyme inhibitor preserves autonomic reflex control, with favorable consequences for cardiovascular homeostasis.

Sympathetic and reflex alterations in systo-diastolic and systolic hypertension of the elderly

Background Previous studies have shown that young and middle-aged essential hypertensives are characterized by a sympathetic activation coupled with an impaired baroreflex-heart rate control. The present study aimed to determine whether these neuroadrenergic and reflex alterations also characterize systo-diastolic and systolic hypertension of the elderly. Subjects and methods In 20 untreated elderly essential hypertensive subjects [10 with a systo-diastolic and 10 with an isolated systolic hypertension, aged 67.2 ± 1.5 years and 66.9 ± 1.7 years (mean ± SEM)], we measured beat-to-beat arterial blood pressure (finger photoplethysmographic device), heart rate (electrocardiogram) and efferent postganglionic muscle sympathetic nerve activity (microneurography) at rest and during baroreceptor stimulation and deactivation induced by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Data were compared with those obtained in 11 age-matched normotensive control subjects. Results Compared to the elderly normotensive group, muscle sympathetic nerve activity was increased to a similar degree in the group of systo-diastolic and systolic hypertension (50.8 ± 4.2 versus 75.2 ± 5.2 and 70.4 ± 5.1 bursts per 100 heart beats, respectively, P <0.01 for both). In the control group, the stepwise increase in arterial pressure induced by phenylephrine caused progressive bradycardia and sympathoinhibition, while the stepwise decrease in arterial pressure had opposite effects. While baroreceptor-heart rate control was markedly impaired (average reduction 41.6%), in both systo-diastolic and systolic hypertensive patients, baroreceptor modulation of sympathetic nerve traffic was similar to that seen in normotensive individuals. Conclusions These data demonstrate that sympathetic activation is not only a feature of young and middle-aged, but also of elderly hypertensives, regardless of whether both systolic and diastolic or only systolic blood pressure is increased. They also show that hypertension of the elderly is not accompanied by an impaired baroreceptor modulation of sympathetic nerve traffic.

Fluctuations of Radial Artery Distensibility Throughout the Menstrual Cycle

Estrogen administration has a number of favorable cardiovascular effects, and recent evidence suggests that these include an increase in arterial distensibility. Whether this is also the case for the physiological changes in estrogen production during the menstrual cycle has never been determined, however. In 21 premenopausal healthy women, we continuously measured radial artery diameter and blood pressure by an echo-tracking device and a beat-to-beat finger device, respectively. Arterial distensibility was calculated as distensibility/blood pressure curve. The measurements were made during the follicular, ovulatory, and luteal phases of the menstrual cycle. As expected, compared with the follicular phase, plasma estradiol, follicle-stimulating hormone, luteinizing hormone, and prolactin were increased in the ovulatory phase, whereas progesterone was increased in the luteal phase, together with antidiuretic hormone. Radial artery distensibility was increased in the ovulatory and reduced in the luteal phase, the changes being independent of the small, concomitant blood pressure changes. The arterial wall stiffening seen in the luteal phase was associated with a reduction in the flow-dependent endothelial dilatation of the radial artery as assessed by the hyperemia after short-term ischemia of the hand. Thus, the natural menstrual cycle is characterized by alterations in radial artery distensibility. The mechanisms responsible for this phenomenon remain to be clarified. It is possible, however, that the greater arterial distensibility of the ovulatory phase is due to an estrogen-dependent reduction in vascular smooth muscle tone, whereas the arterial stiffening of the luteal phase depends on vascular smooth muscle contraction due to more complex hormonal phenomena, ie, an endothelial impairment due to estrogen reduction but also to an increase in progesterone and antidiuretic hormone levels.

Alterations of radial artery compliance in patients with congestive heart failure

Congestive heart failure is accompanied by several hemodynamic alterations. To investigate whether these alterations include reduced arterial compliance, we studied 25 patients (age 57 +/- 2 years, mean +/- SE) with a mild or severe congestive heart failure based on clinical symptoms (New York Heart Association class II vs III or IV) and on echocardiographic alterations of left ventricular diastolic diameter and ejection fraction. Radial artery diameter and blood pressure were continuously measured by Doppler ultrasonography and a finger pressure device, respectively. Compliance was calculated by the Langewouters formula, and compliance values were derived throughout the systolic-diastolic pressure range. The area under the compliance-pressure curve normalized for pulse pressure was used to compare compliance values in the various groups. Data were obtained both in baseline condition and at the release from a 12-minute brachial artery occlusion. Fourteen healthy, age-matched subjects served as controls. Compared with the control group, patients with severe congestive heart failure showed a reduction of baseline compliance index (-48%, p < 0.01). Furthermore, while in control subjects compliance markedly increased after brachial artery occlusion (+43%, p < 0.01), in patients with severe congestive heart failure no increase occurred. No baseline compliance alteration was seen in patients with mild congestive heart failure in whom, however, the postischemic increase in compliance was also significantly blunted (-50% vs controls, p < 0.05). Thus, arterial compliance and arterial compliance modulation are impaired in congestive heart failure. Although more marked in severe congestive heart failure, the impairment is manifest in mild congestive heart failure as well.

Sympathetic and reflex abnormalities in heart failure secondary to ischaemic or idiopathic dilated cardiomyopathy

Congestive heart failure (CHF) is characterized by a sympathetic activation and a baroreflex impairment whose degree is directly related to the clinical severity of the disease. However, whether these abnormalities vary according to the ischaemic or idiopathic dilated nature of the CHF state has not been conclusively documented. In patients with a clinically stable, chronic CHF state in New York Heart Association functional class II and III, due either to ischaemic heart disease (IHD; n=22, age 60.3+/-2.4 years, means+/-S.E.M.) or to idiopathic dilated cardiomyopathy (IDC; n=20, age 58.9+/-2.8 years), and in 30 age-matched controls, we measured arterial blood pressure (using a Finapres device), heart rate (by electrocardiogram) and postganglionic muscle sympathetic nerve traffic (by microneurography) at rest and during baroreceptor manipulation induced by the vasoactive drug-infusion technique. Blood pressure values were not significantly different in CHF patients and controls. Compared with controls, heart rate was similarly increased and left ventricular ejection fraction (by echocardiography) similarly reduced in CHF patients with IHD or IDC. Muscle sympathetic nerve traffic was significantly greater in CHF patients than in controls, and did not differ between patients with IHD or IDC (67.3+/-4.2 and 67.8+/-3.8 bursts/100 heart beats respectively). This was also the case for the degree of baroreflex impairment. These data show that CHF states due to IHD or to IDC are characterized by a similar degree of peripheral sympathetic activation and by a similar impairment of the baroreflex function. Thus the neuroadrenergic and reflex abnormalities characterizing CHF are independent of its aetiology.

Effects of Isolated Systolic Hypertension and Essential Hypertension on Large and Middle-sized Artery Compliance

BACKGROUND Systolic hypertension of the elderly is characterized by a reduction in arterial compliance. Whether and to what extent this involves arteries of various structure and size is not well known. OBJECTIVE To study carotid and radial artery compliance in systolic hypertension of the elderly, compared to essential hypertension and normotension. METHODS We investigated 28 elderly patients with systolic hypertension (age 68.6 +/- 1.4 years, mean +/- SE; systolic blood pressure > 160 mmHg and diastolic blood pressure < 90 mmHg) plus 17 age-matched patients with essential hypertension and 15 age-matched healthy normotensive subjects. Radial and carotid artery compliance were evaluated using echotracking techniques. In both arteries compliance was assessed statistically and dynamically, i.e. as compliance values throughout the diasto-systolic pressure range. Measurements included intima-media wall thickness of the radial artery. RESULTS Compared to normotensive subjects, carotid artery compliance was reduced in essential hypertension and more so in systolic hypertension. However, although in both groups radial artery wall thickness was markedly greater than in the normotensive group, radial artery compliance was markedly reduced in systolic hypertension, but unchanged in essential hypertension. CONCLUSIONS In systolic hypertension of the elderly the reduction of arterial compliance is marked in both muscular and large elastic arteries, while in elderly essential hypertensives changes in arterial compliance are more heterogeneous, i.e. only carotid artery compliance is reduced. The different effects of these two types of hypertension on arterial mechanics are visible throughout the physiological range of blood pressure and probably accounted for by different alterations in vessel wall structure.

Cardiac and vascular structural changes in normotensive subjects with parental hypertension

Objective To evaluate whether a predisposition to hypertension is associated with early cardiac and vascular alterations. Subjects Twenty-five normotensive subjects with both parents hypertensive (group 1) and 28 age- and sex-matched control subjects with both parents normotensive (group 2). Methods In the two groups the measurements included: clinic blood pressure; left ventricular end-diastolic diameter, septal wall thickness and posterior wall thickness (by echocardiography); minimal forearm and calf vascular resistances (i.e. resistance assessed immediately after prolonged ischaemia, which depends on arteriolar wall thickness); and baseline and postischaemic radial artery compliance-pressure curves over the systolodiastolic pressure range (by echotracking device and finger blood pressure). Results Group 1 had a slightly higher clinic blood pressure, and septal and posterior wall thickness, than group 2. Minimal forearm vascular resistance was clearly greater in group 1 than in group 2, whereas minimal calf vascular resistance was not significantly different in the two groups. Radial artery compliance was also similar in the two groups. Conclusions Parental predisposition to hypertension is accompanied by cardiac and arteriolar structural changes qualitatively similar to those found in hypertensive patients, although arteriolar structural changes do not involve all vascular beds. Arterial compliance is not altered in this condition. Vascular changes may be determined by mechanisms other than blood pressure elevation.