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Biomedical subjects

N Benjamin

Publications and source records attributed to N Benjamin.

104 records · Page 6Linked to original sources
PubMed1988

Verapamil and bendrofluazide in the treatment of hypertension: a controlled study of effectiveness alone and in combination.

The effects of verapamil and bendrofluazide used singly and in combination were examined in patients with primary hypertension in a patient blind, partly observer blind placebo controlled study of parallel group design; there were ten subjects in each arm of the trial. Verapamil 160 mg twice daily caused supine mean arterial pressure to fall by 21 mmHg; this reduction was significantly greater (p less than 0.05) than that induced by bendrofluazide 5 mg daily which caused a fall of only 10 mmHg. The addition of verapamil 160 mg twice daily to bendrofluazide 5 mg daily caused a further fall in pressure of 18 mmHg (p less than 0.005), but the reduction in pressure when bendrofluazide was added to verapamil was only 1 mmHg and not significant. Bendrofluazide therapy caused a fall in plasma potassium concentration and an increase in plasma urate concentration; urinary calcium excretion was reduced. Verapamil caused no detectable biochemical alterations in plasma or urine.

Adult↗
PubMed1988

Angiotensin II augments sympathetically induced venoconstriction in man.

1. The constriction produced by a single deep breath was measured simultaneously in two adjacent hand veins in normal volunteers. One vein was infused with angiotensin II (ANG II) while the other acted as a control. 2. At a dose lower than that required to produce direct venous constriction (1 pmol/min), ANG II significantly augmented the constriction caused by a deep breath in eight subjects (P less than 0.01). The same dose had no effect on the venoconstriction caused by infused noradrenaline (NA) in a further six subjects. 3. It is concluded that ANG II at low doses may cause venoconstriction indirectly by augmenting sympathetically induced venous tone via a presynaptic mechanism. This observation may help to explain the apparent venodilating property of angiotensin-converting enzyme inhibitors in clinical situations where the renin-angiotensin system is stimulated.

Adult↗
PubMed1988

Sympathetically mediated vasoconstriction is augmented by angiotensin II in man.

In order to determine whether angiotensin II may influence sympathetically mediated arteriolar constriction in man, we have examined the effect of angiotensin II, infused directly into the left brachial artery of normal subjects, on the reduction in forearm blood flow produced by a lower-body negative pressure (LBNP) of 15 mmHg. Angiotensin II (320 fmol/min) caused no reduction in blood flow when given alone but significantly augmented the reduction in blood flow in response to LBNP. The same dose of angiotensin II did not affect a similar reduction in forearm blood flow produced by infused noradrenaline (12.5-50 ng/min). We conclude that angiotensin II augments sympathetically mediated constriction of resistance vessels in man at concentrations with no direct effect on vessel tone. The lack of an effect of angiotensin II on constriction in response to infused noradrenaline suggests the involvement of a presynaptic mechanism.

Angiotensin II↗
PubMed1988

Is the increased responsiveness to verapamil in the forearm resistance vessels of patients with hypertension a consequence of structural change?

A mathematical model has been developed that relates wall tension in resistance vessels to changes in both distending pressure and flow; the effect of alterations in wall: lumen ratio is taken into account. The model indicates that increased autoregulatory activity in the forearm circulation of patients with primary hypertension could result from an increased response of the vascular smooth muscle to increased intraluminal pressure, but it could be accounted for by an increase in wall:lumen ratio from about 0.2 to 0.3. When the effect of the same increase in wall:lumen ratio on response to dilator agents is examined, it appears that the enhanced response to verapamil could be accounted for by structural change and there is no need to postulate a functional change. If this view is correct, however, it becomes necessary to assume a reduced response of the vascular smooth muscle to sodium nitroprusside in patients with hypertension if the unchanged dilator effect of this drug is to be explained.

Dose-Response Relationship, Drug↗
PubMed1988

Vascular responses to local atrial natriuretic peptide infusion in man.

1. The effect on skin and muscle blood flow of arterial infusion of atrial natriuretic peptide (ANP) directly into the forearm circulation, and on venous tone of direct infusion into a dorsal hand vein, was studied in normal subjects. 2. ANP produced a dose-dependent increase in both skin and muscle blood flow, but at equivalent doses, produced no dilatation of noradrenaline-preconstricted dorsal hand veins. These findings indicate that ANP acting locally, is an arterioselective dilator in the upper limb circulation in normal man. 3. Measurements of ANP in venous plasma during arterial infusion suggest marked clearance of ANP across the forearm vascular bed. Such peripheral clearance may, at least in part, account for the short plasma half-life of this peptide. 4. The lowest dose of ANP infused was calculated to produce plasma levels similar to those found in patients with heart failure. The findings with this dose suggest that, in heart failure, circulating levels of ANP may be within a range capable of influencing peripheral vascular resistance directly.

Adult↗
PubMed1988

Vasodilatation by calcitonin gene-related peptide and by substance P: a comparison of their effects on resistance and capacitance vessels of human forearms.

A comparison has been made of the effects of the potent vasodilating peptide calcitonin gene-related peptide (CGRP) and substance P (SP) on resistance and capacitance vessels of normal subjects. Brachial artery infusion of 1.25 to 10 pmol/min CGRP and of 0.25 to 1.5 pmol/min SP produced maximal increases in forearm blood flow (177 +/- 75% and 198 +/- 50%, respectively), as measured by venous occlusion plethysmography. The vasodilation due to CGRP was prolonged, with a half-life of biological effect of approximately 18 min, while that due to SP was of short duration, with a half-life of biological effect of approximately 15 sec. There was rapid development of tachyphylaxis to the effects of arterial infusion of SP, but not of CGRP, during a prolonged infusion at one dose. CGRP did not alter the diameter of a superficial hand vein, either at rest or when the vein was constricted by a simultaneous infusion of norepinephrine or by the single deep breath reflex. In contrast, SP caused dilatation of veins preconstricted with norepinephrine, although the effect was only transient and dose-response curves could not be constructed. The venoconstrictor response to a single deep breath was abolished by SP. Simultaneous arterial infusion of both peptides produced at least additive, and possibly synergistic, effects on forearm blood flow. We propose that both CGRP and SP have a role in the regulation of vascular smooth muscle tone.

Adult↗
PubMed1984

Small increments in plasma calcium concentration reduce the responsiveness of forearm resistance vessels to verapamil in men with primary hypertension.

The effect on the forearm resistance vessels of small increases in the local plasma concentration of calcium and magnesium has been examined in 20 men with primary hypertension. Studies were carried out by a standard plethysmographic method with infusion of drugs into the brachial artery. Infusion of calcium at 10 mumol/min into the forearm caused basal blood flow to fall by 9% (n = 17;0.1 greater than P greater than 0.05) and the dilator response to verapamil to fall by 28% (P less than 0.005). Infusion of magnesium at the same rate caused basal blood flow to rise by 22% (n = 12; P less than 0.05), but the dilator response to verapamil was not significantly changed. The response of the resistance vessels to verapamil is known to be enhanced in patients with hypertension, and the results show that this response is attenuated by a small increase in the local calcium concentration. The findings are consistent with the view that altered handling of calcium by the cell membrane contributes to the functional abnormality of the hypertensive resistance vessel.

Adult↗
PubMed1977

Placental transfer of a large angiotensin fragment in the guinea pig.

Angiotensin II (AII) levels are usually higher in the fetal than in the maternal circulations. Radioiodinated AII has been used to establish whether or not this hormone crosses the placenta from the fetus to the mother in the pregnant guinea pig. No intact radioiodinated AII was found to have crossed in any of 13 experiments. A single radioiodinated AII fragment was found in 10 of these experiments. This ran as (des-(Asp1 Arg2 Val3)) in one solvent, but this could not be confirmed when a different solvent was used. The results support the hypothesis, previously based on indirect evidence, that AII does not cross the placenta.

Angiotensin II↗
PubMedDate not supplied

Detection of nitric oxide and nitric oxide synthases in psoriasis.

Biopsies from psoriasis lesions and clinically uninvolved skin of eight patients and five normal subjects were studied by immunocytochemistry with computerized image analysis for the presence of endothelial, neuronal and inducible isoforms of nitric oxide synthase. Endothelial nitric oxide synthase was expressed in the endothelium and weakly in some keratinoctyes. Its expression was not significantly different in psoriasis. Inducible nitric oxide synthase, however, was absent from normal skin but was significantly upregulated in psoriatic lesional skin, focally in keratinocytes but to the greatest extent in the papillary dermis and to a lesser extent in clinically uninvolved psoriatic skin. Inducible nitric oxide synthase staining was greatest in the more severe lesions and correlated with the inflammatory infiltrate (CD3-positive cells) and with keratinocyte proliferation (Ki-67-positive cells). In normal skin, neuronal nitric oxide synthase was expressed only in keratinocytes in the granular layer and eccrine sweat glands. However, in psoriasis and clinically uninvolved skin the neuronal form was present through all levels of the epidermis. Direct measurement of nitric oxide production from the skin surface revealed a tenfold increase in the lesions of 16 psoriatic patients compared with their nonlesional skin, and this nitric oxide production was inhibited by topical betamethasone.

Adult↗
PubMedDate not supplied

A topical nitric oxide-generating therapy for cutaneous leishmaniasis.

Nitric oxide (NO) synthesized by macrophages is cidal to Leishmania. Since NO diffuses into tissues, we reasoned that NO-generating creams applied topically to lesions might be an effective and inexpensive treatment for cutaneous leishmaniasis (CL). NO was generated non-enzymatically by the acidification of nitrite (KNO2) by ascorbic acid (ASC) or salicylic acid (SAL). Experiments in vitro showed that the combinations of KNO2 and SAL, ASC, or KC1 all killed promastigotes and amastigotes of L. major in a dose- and time-dependent manner, but were toxic to macrophages at higher concentrations. Experiments in vivo showed modest efficacy of the combinations applied topically to L. major CL lesions of BALB/c mice. Forty patients with parasitologically proven L. tropica CL from Aleppo, Syria, were treated for 4 weeks with KNO2 in aqueous cream combined with KC1, ASC, or SAL. Only 11 (28%) of 40 patients showed improvement and only 5 (12%) of 40 were cured at 2 months. Further development of NO-generating creams is warranted.

Administration, Topical↗
PubMedDate not supplied

Inhaled nitric oxide as therapy for pulmonary hypertension in postoperative cases of congenital heart defects.

This is a prospective study using inhaled nitric oxide (NO) as a selective pulmonary vasodilator in postoperative cases of CHD. From February 1995 to December 1995, NO was used selectively in 10 patients postoperatively in whom conventional management of PAH crisis failed and PA pressures were more than half the systemic pressure. The age of the patients varied from 2 months to 3 years and duration of NO inhalation ranged from 1 day to 13 days. Of 10 patients, 8 patients responded well with 5-20 ppm and 2 did not respond, even after increasing the NO to 120 ppm. The preoperative mean pulmonary systolic pressure was 83 +/- 17.1 mm Hg against mean systemic systolic pressure of 84 +/- 9.2 mm Hg. Postoperatively, their PA pressure reduced to 54 +/- 16.1 mm Hg (mean systolic) with systemic pressure of 85 +/- 15.9 mm Hg (mean systolic). After using inhaled NO, PA pressure dropped to 19 +/- 2.5 mm Hg mean systolic (p < 0.0078), after excluding the nonresponders. The two nonresponders died postoperatively. Our study shows that NO selectively reduces the PA pressure unlike conventional vasodilators. This helps to decrease the incidence of postoperative PAH crisis, thereby reducing the morbidity and mortality. However, long-term beneficial effects are yet to be studied.

Administration, Inhalation↗