Lisinopril improves aortic compliance and renal flow. Comparison with nifedipine.

We compared the systemic and regional hemodynamic effects of nifedipine and lisinopril in 26 elderly hypertensive patients with the use of the pulsed Doppler ultrasound technique. Nifedipine is a dihydropyridine calcium antagonist, and lisinopril is an angiotensin-converting enzyme inhibitor. The study had a single-blind crossover design: nifedipine and lisinopril were given for 8 weeks each after washout periods of 4 weeks. Both nifedipine and lisinopril significantly reduced mean arterial pressure to the same extent (P < .01); cardiac output remained unchanged in both nifedipine- and lisinopril-treated groups. Lisinopril increased renal flow significantly (P < .01), but nifedipine did not. Common carotid, vertebral, celiac, and superior mesenteric arterial and diaphragmatic and terminal aortic flows did not show a significant change with either nifedipine or lisinopril. The specific action of lisinopril on the thoracic aorta was a marked improvement of aortic compliance compared with nifedipine, which might be partly responsible for an increase in renal flow. Lisinopril may provide more desirable regional hemodynamic effects and additional benefits for elderly hypertensive patients.

Time course of hemodynamic responses to sodium in elderly hypertensive patients.

Thirty-one patients with essential hypertension (81.6 +/- 6.9 years old) were studied during two different regimens of sodium intake: 120 meq/day for 8 weeks and 344 meq/day for 2 weeks. Systemic hemodynamic data were measured with Doppler echocardiography from which the mitral flow velocity integral, cardiac index, and total peripheral resistance were calculated. The salt-sensitive patients in whom the increase in total peripheral resistance was greater than the increase in cardiac index with salt loading were termed SST. In the salt-sensitive patients termed SSC, the increase in cardiac index was greater than the increase in total peripheral resistance with increased sodium intake. All SST patients on day 7 of the high sodium diet remained in the SST group on day 14. Nine of 13 patients in the SSC group on day 7 remained in the SSC group on day 14, and the remaining four patients in the SSC group on day 7 fell into the SST group on day 14. Four of eight non-salt-sensitive (NSS) patients on day 7 of the high salt regimen remained in the NSS group on day 14, whereas the remaining four patients in the NSS group on day 7 fell into the SSC group on day 14. Our data suggest a changing pattern with sodium loading of initially high cardiac index followed by a persistently raised total peripheral resistance. The celiac, superior mesenteric, and renal arteries vasoconstricted with sodium repletion in both SST and SSC patients. With salt loading, the terminal aortic vascular bed vasodilated in the SSC patients and vasoconstricted in the SST patients.

Lisinopril reverses left ventricular hypertrophy through improved aortic compliance.

We treated with nifedipine or lisinopril 38 essential hypertensive patients with left ventricular hypertrophy. The study had a single-blind crossover design; nifedipine or lisinopril was given for the first 24 weeks, and then patients were crossed over to the other antihypertensive agent for another 24 weeks. Both nifedipine and lisinopril significantly decreased mean arterial pressure to the same extent. Although lisinopril decreased left ventricular mass index more rapidly than nifedipine, 48 weeks of antihypertensive treatment with nifedipine or lisinopril reduced the extent of left ventricular hypertrophy to the same level. Stepwise multiple linear regression analysis revealed that the reversal of left ventricular hypertrophy may be mainly due to a reduction in mean arterial pressure during the 24-week nifedipine treatment and due to an improvement of aortic compliance during the lisinopril treatment. Both nifedipine and lisinopril are effective in the reversal of hypertensive left ventricular hypertrophy; however, the agents have disparate actions on hemodynamic factors.

Plasma norepinephrine is a major determinant of hemodynamic alterations with sodium loading.

OBJECTIVE: To assess hemodynamic responses to 3 weeks of sodium loading and to evaluate factors which contribute to hemodynamic alterations. DESIGN: Analysis of patients' central hemodynamic and laboratory variables before and after sodium loading. SETTING: A referral centre. PATIENTS: Thirty-one elderly hypertensives. INTERVENTIONS: Doppler flowmetry and laboratory examinations were performed during different sodium intake; 120 mmol/day for 8 weeks and 344 mmol/day for 3 weeks. RESULTS: Patients were divided into three groups; those in whom sodium loading increased total peripheral resistance (SST); those in whom salt repletion increased cardiac index (SCC); a non-salt-sensitive group (NSS). The overwhelming reaction to salt loading is that, with time, the NSS and SSC groups became part of the SST group. When the SSC patients became SST with sodium loading, serum sodium and plasma arginine vasopressin decreased and haematocrit increased, suggesting that the excretion of sodium and water accompanied with a decrease in circulating plasma volume may be responsible for the hemodynamic alteration from SSC to SST. In those who remained in the SSC group throughout the 3 weeks of salt repletion, plasma norepinephrine decreased on all of days 7, 14 and 21 of the high-sodium diet compared with the regular-sodium regimen, whilst in patients in the SST group on day 21 of the high-sodium diet plasma norepinephrine remained unchanged throughout the 3 weeks of salt loading. CONCLUSIONS: We confirmed a changing pattern of initially high cardiac index giving way to a persistently elevated total peripheral resistance with sodium loading. Plasma norepinephrine proved to be the best predictor of which subjects were or became SST.

Participation of protein kinase C in endothelin-1-induced contraction in rat aorta: studies with a new tool, calphostin C.

1. Calphostin C at 10(-6) M was shown to be selective and highly effective in inhibiting contractile responses of rat aortae to 12-o-tetradecanoylphorbol-13-acetate, while it had no effect on contractile responses to elevated KCl. 2. In the rat aorta, endothelin-1 (ET-1) developed a sustained tonic contraction dose-dependently in both normal Ca(2+)-containing Krebs and Ca(2+)-free Krebs containing 1 mM EGTA. Calphostin C (10(-6) M), a selective protein kinase C inhibitor, antagonized the maximal tensions for cumulative addition of 10(-8) M ET-1 by 13.2% in Ca(2+)-containing medium and 25.8% in Ca(2+)-free Krebs containing 1 mM EGTA. 3. In both Ca(2+)-containing medium and Ca(2+)-free Krebs containing 1 mM EGTA, precontraction with 10(-8) M ET-1 had no effects on the contractile response to subsequently added 10(-6) M 12-o-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C. 4. In Ca(2+)-free Krebs containing 1 mM EGTA, precontraction with 10(-6) M TPA potentiated the contractile response to subsequently added 10(-8) M ET-1, whereas this potentiation was abolished by pretreatment with 10(-6) M calphostin C. The mechanism of the TPA-induced potentiating effect remains to be determined. 5. These results suggest that the participation of protein kinase C in the 10(-8) M ET-1-induced contraction may be 13.2% and 25.8% in the presence and absence of extracellular Ca2+, respectively, and that mechanisms other than protein kinase C may be predominantly responsible for ET-1-induced tonic contraction.

Therapeutic effect and mechanism of repetitive transcranial magnetic stimulation in Parkinson's disease.

The therapeutic effect of repetitive transcranial magnetic stimulation (rTMS) on clinical performance was assessed by a double-blind study in 9 patients with Parkinson's disease (PD). Nine other patients underwent sham stimulation as controls. The modified Hoehn and Yahr (H&Y) staging scale, the Schwab and England Activities of Daily Living (ADL) scale, and the Unified Parkinson's disease rating scale (UPDRS) were used to assess changes of clinical performance. Patients were assessed prior to and following 2 months of rTMS. In addition, the mechanism of rTMS was investigated by dopamine and homovanillic acid (HVA) in the lumbar cerebrospinal fluid (CSF) of 17 patients before and after therapeutic rTMS for three or four months. rTMS was applied manually to the frontal areas 60 times per session, i. e., 30 times per side using a large circular coil, a pulse intensity of 700 V, and a frequency of 0.2 Hz. Sessions were continued once a week for 2 months. The 9 control patients showed no changes of symptoms between the initial evaluation and that after 2 months of sham rTMS. In contrast, all 9 patients receiving rTMS showed a significant decrease of the modified H&Y and UPDRS scores after 2 months, while the Schwab and England ADL Scale scores increased significantly. In the second CSF sample from patients receiving rTMS, HVA showed a significant decrease These results suggest that rTMS is beneficial for the symptoms of Parkinson's disease and that it may act via inhibition of dopaminergic systems.

Pharmacological assessment of Ca2+ dependence of endothelin-1-induced response in rat aorta.

In rat aorta, endothelin-1 (ET-1) induced a slowly developing and sustained contraction in Ca(2+)-containing normal Krebs, nominally Ca(2+)-free Krebs, and Ca(2+)-free Krebs containing EGTA with a decreasing level of contraction. When ET-1-precontracted tissues were washed with Ca(2+)-free Krebs +50 microM EGTA, the tissues spontaneously and slowly relaxed. Readministration of Ca2+ during the early spontaneous relaxation phase caused a rapidly developing tonic contraction. When added during the late spontaneous relaxation phase, Ca2+ evoked slowly developing or, sometimes, biphasic contractions. In the presence of sarcoplasmic reticulum Ca(2+)-pump inhibitor, cyclopiazonic acid, the above biphasic contraction brought about by readministration of Ca2+ converted to a rapidly developing monophasic response. Thus, the first component of the biphasic contraction may be due to refilling of ET-1-sensitive Ca2+ store via the internal membrane Ca(2+)-pump. Furthermore, the ability of the phenylephrine-sensitive pool of internal Ca2+ to refill in the presence of 10(-8) M ET-1 suggests that the phenylephrine-sensitive pool differs from ET-1-sensitive pool and cannot be depleted by ET-1.

Terminal aortic response to sodium intake is the major determinant of total peripheral resistance in elderly hypertensives.

Thirty-four elderly patients were studied using a Doppler flowmeter during different sodium intakes. Salt increased mean blood pressure and cardiac output (CO), while total peripheral resistance (TPR) remained unchanged. Neither carotid nor terminal aortic resistance changed, while coeliac, superior mesenteric or renal resistance increased. There was a significant and direct correlation (r = 0.82) between the change in TPR and that in terminal aortic resistance. Salt-sensitive patients were divided into two subgroups; the SST group in which sodium loading increased TPR more than CO, and the SSC group in which salt loading increased CO more than TPR. Terminal aortic resistance increased in the SST, decreased in the SSC, and remained unchanged in the non-salt-sensitive group with salt loading. The terminal aortic vascular bed received much of the increase of CO in the SSC patients. In the SST group, the contribution of the individual vascular area to increased TPR was assessed, which revealed that terminal aortic response to sodium loading was the major determinant of increased TPR. We concluded that the responses of terminal aortic vascular bed to sodium loading contributed to the changes in TPR.

Nilvadipine increases cerebral blood flow in elderly hypertensives: comparison with nifedipine.

We compared haemodynamic and humoral responses to nifedipine and nilvadipine in 25 elderly hypertensives. The study had a single-blind crossover design. Doppler flowmetry and laboratory examinations were performed before and after nifedipine and nilvadipine. Both nifedipine and nilvadipine significantly reduced mean arterial pressure to the same extent. Nilvadipine increased cardiac output, carotid flow and vertebral flow whereas nifedipine had no significant effect on either cardiac output or regional blood flows. Nilvadipine increased plasma atrial natriuretic peptide and decreased plasma noradrenaline. In the nilvadipine group, the relations between changes in these humoral parameters and those in cardiac output suggest that an elevation of pre-load may play a role in increasing cardiac output. The effects of nilvadipine on cerebral perfusion might provide additional benefits for the elderly hypertensives.

Relationship between intracellular Ca2+ store and protein kinase C in agonist-induced contraction of hypertensive rat aortae.

The roles of intracellular Ca2+ store and protein kinase C (PKC) in vascular contractile responses independent of Ca2+ influx were studied using aortic rings from spontaneously hypertensive rat (SHR) and Wistar-Kyoto rat (WKY). The functional sizes of agonist-sensitive intracellular Ca2+ store were estimated as the peak response to agonist after PKC inhibition with calphostin C (Cal-C), a PKC inhibitor. The participation of PKC in 5-hydroxytryptamine-, phenylephrine-, and endothelin-1 (ET-1)-induced contractions in aortae of SHR was equal to, or greater than that in WKY. In contrast, compared with WKY, SHR aortae possessed a greater size of endothelin-1-sensitive Ca2+ store, a similar size of 5-hydroxytryptamine-sensitive Ca2+ store, and a smaller size of phenylephrine sensitive Ca2+ store. Based on these data, both PKC activation and functional size of intracellular Ca2+ store differ between SHR and WKY and these differences are selective among agosists.

Does juxtamesenteric placement of intra-aortic balloon interrupt superior mesenteric flow?

To assess influences of intra-aortic balloon pumping (IABP) on superior mesenteric flow, 15 postoperative patients were examined, in whom distal aspects of balloons were distal to the superior mesenteric artery. Superior mesenteric flow velocity-time integral in systole (IntS), that in diastole (IntD), and the sum of IntS and IntD (IntS+IntD) were determined on and off IABP (IABP ON-OFF test). The same parameters were obtained with balloon inflating on every other beat (IABP 1:2 test). The cardiac cycle with balloon inflation during diastole was defined as "1:2 ON," and the cardiac cycle without balloon inflation during diastole was defined as "1:2 OFF." (1) IABP ON-OFF test. IABP increased IntS (p less than 0.01), IntD (p less than 0.01), IntS+IntD (p less than 0.01), and cardiac output (p less than 0.05). The increments in IntS, IntD and IntS+IntD on IABP are attributed largely to an increased in cardiac output. (2) IABP 1:2 test. IntS during 1:2 OFF was greater than IntS during 1:2 ON (p less than 0.01), whereas IntD during 1:2 OFF was smaller than IntD during 1:2 ON (p less than 0.01). There was no significant difference in IntS+IntD between 1:2 ON and 1:2 OFF. These data suggest that juxtamesenteric balloon placement did not interrupt the arterial inflow of a superior mesenteric artery.

Hemodynamic characteristics of conscious deoxycorticosterone acetate hypertensive rats.

An electromagnetic flow probe was chronically implanted around the common carotid, superior mesenteric, or renal artery or the terminal aorta in deoxycorticosterone acetate (DOCA) hypertensive rats (prepared with DOCA and saline after uninephrectomy) and uninephrectomized control rats. A catheter for pressure measurement was inserted into the terminal aorta through a femoral artery. At rest the carotid and hindquarter (measured at the terminal aorta) blood flows in DOCA hypertensive rats were similar to the respective, corresponding values in normal rats with intact bilateral kidneys. The group mean of superior mesenteric flow was about 70% and that of renal flow about 40% larger than in normal rats. Cardiac output was estimated to be greater in DOCA hypertensive rats than in normal rats. In uninephrectomized control rats, superior mesenteric flow was larger than in normal rats to such an extent that an increase in cardiac output was assumed as in DOCA hypertensive rats, but renal flow was normal (about twice the unilateral renal flow in normal rats). Estimation of regional sympathetic vasoconstrictor tone from the decrease in peripheral resistance with hexamethonium and vasopressin antagonist revealed a substantial tone also in the superior mesenteric and hindquarter areas, where the tone was estimated to be almost absent in normal rats and uninephrectomized rats. It is suggested that hypertension in DOCA hypertensive rats is sustained by an increase in cardiac output and an elevation of vasoconstrictor tone in resistance vessels. Since increase in cardiac output appears to be similarly present in uninephrectomized control rats, the elevation of sympathetic tone due to administration of DOCA and salt seems to be indispensable for DOCA hypertension.

Acute effects of captopril on blood pressure and regional blood flows in two types of renovascular hypertensive rats in conscious state.

Mean arterial pressure and three regional blood flows--renal, superior mesenteric, and hindquarter flows--were monitored in conscious normotensive control rats (NCR), in two-kidney, one-clip (two-kidney), and in one-kidney, one-clip (one-kidney) hypertensive rats. After administering captopril, an angiotensin-converting enzyme inhibitor, mean arterial pressure decreased in all three groups. However, lowering of arterial pressure was not statistically significant in any of the groups. Renal flow increased significantly in the intact artery of two-kidney hypertensive rats, whereas it did not significantly increase in the clipped artery of one-kidney hypertensive rats and in the intact artery of NCR. Superior mesenteric flow increased significantly only in one-kidney hypertensive rats. Hindquarter flow did not significantly change in the three groups. Regional resistance reduced significantly in not only renal but also in superior mesenteric vascular area in two-kidney hypertensive rats, whereas it did not reduce significantly in these two vascular areas in one-kidney hypertensive rats and in NCR. The present findings show that the renin-angiotensin-mediated vasoconstriction plays a role in not only renal but also in superior mesenteric vascular area in two-kidney hypertensive rats, whereas it hardly plays a role in these three vascular beds in one-kidney hypertensive rats.

Pathologic and imaging findings of an oncocytoma in the deep lobe of the left parotid gland.

Oncocytoma is a rare salivary gland tumour consisting of oncocytes with many hyperplastic mitochondria. It usually occurs in the parotid gland. Because the features of oncocytoma resemble those of other benign and low-grade-malignant salivary gland tumours, clinical diagnosis is often challenging. This report presents the pathologic and imaging findings of an oncocytoma arising in the deep lobe of the left parotid gland in a 66-year-old man. Oncocytoma was diagnosed on the basis of histological, magnetic resonance imaging, and scintigraphic findings. The tumour showed accumulation of technetium-99m pertechnetate and decreased signal intensity on both T1- and T2-weighted magnetic resonance images.

Annular pustular psoriasis associated with affective psychosis.

An eighty-year-old man presented with recurrent annular erythema with pustules on the axillae, trunk, and groin consistent with a diagnosis of annular pustular psoriasis. Over the years, exacerbations of his skin lesions directly followed manic episodes. Use of major tranquilizers, including chlorpromazine, brought about a favorable remission of both the manic symptoms and the cutaneous lesions.

Differentiation of disseminated superficial actinic porokeratosis from the superficial disseminated eruptive form of porokeratosis of Mibelli.

Two cases of porokeratosis are reported here, one of which can be classified as the superficial disseminated form of porokeratosis of Mibelli and the other as disseminated superficial actinic porokeratosis. The relationship between these two diseases is discussed briefly.

[Therapeutic effect of repetitive transcranial magnetic stimulation in Parkinson's disease].

The therapeutic effect of repetitive transcranial magnetic stimulation (r-TMS) on clinical performance was studied in 8 patients with Parkinson's disease (PD). Seven patients were used as controls and underwent sham stimulation. The modified Hoehn and Yahr (H & Y) Staging Scale, Schwab and England Activities of Daily Living (ADL) Scale and Unified Parkinson's Disease Rating Scale (UPDRS) were used to assess changes in clinical performance. Eight patients were assessed prior to and following 3, 6 and 9 months of R-TMS. R-TMS was applied manually 60 times (30 times each side) to the frontal areas using a large circular coil, a pulse intensity of 700 V, and a frequency of 0.2 Hz. Sessions were performed once weekly for 9 months. The 7 control patients showed no differences in clinical symptoms between initial evaluations and evaluations after 3 months of sham R-TMS. In all 8 patients, the modified H & Y staging and UPDRS scores decreased significantly, and the Schwab and England ADL Scale increased significantly after 3, 6 and 9 months of R-TMS therapy. These results suggest that R-TMS is beneficial for the treatment of Parkinsonian symptoms.

Kindler's syndrome.

A 3-year-old girl with congenital poikiloderma had episodic blistering spontaneously or after trauma. Growth and development had been normal. Family history did not show any evidence of cutaneous disease. We believe that this case best fits the designation of Kindler's syndrome.

A case report of substernal goiter.

A case of substernal goiter is reported. A 78-year-old female was admitted to our hospital with no symptoms. Chest roentgenography on admission showed that a mass of 3 by 5 cm in size with calcification located in the substernal region. Computed tomography of the chest and aortography revealed that the mass was attached to the trachea, but the connection to the great vessels was not clear. Pathological findings of the incisional biopsy specimen showed thyroid tissue with no evidence of malignancy. Our clinical diagnosis was substernal goiter. Surgery was not carried out in this case, based on the literature. Surgery is indicated in case of malignancy or in cases with severe illness such as respiratory disorder and superior vena cava syndrome.

[The penetration of cefoperazone into the cerebrospinal fluid in patients on acute or chronic stage].

Cefoperazone (CPZ) was administered to 10 patients with cerebrovascular disturbances at acute and chronic phases to investigate its passage into the cerebrospinal fluid. The antibiotic was administered at dosages of 1 g and 2 g to patients in the acute phase to examine the dose-dependency. The results obtained are summarized as follows: 1. Serum concentrations Peak values of CPZ were 46.9 +/- 4.42 microgram/ml in acute phase patients in 1 g dosage group (acute group 1), 253.1 +/- 63.2 micrograms/ml in acute phase patients in 2 g dosage group (acute group 2), and 197.9 +/- 15.7 micrograms/ml in chronic phase patients in 2 g dosage group (chronic group 2) at 1 hour after CPZ administration. Concentrations of CPZ varied about 5-fold between the 1 g dosage group and the 2 g dosage groups. The acute group 2 showed generally higher values of CPZ concentrations than the chronic group 2. 2. Cerebrospinal fluid concentrations. Peak values were 0.96 +/- 0.30 microgram/ml (at 3 hours) in acute group 1, 4.55 +/- 3.41 micrograms/ml (at 1 hour, except 1 case) in acute group 2, and 1.29 +/- 1.28 micrograms/ml (at 1 hour) in chronic group 2. Acute group 2 showed generally higher values than chronic group 2. 3. CPZ was considered useful for the prevention of postoperative infections in the field of brain surgery.