Increase in Plasma Atrial Natriuretic Peptides during Acute Volume Expansion in Hypertensive Man

ABSTRACT. A new hormonal system originating from cardiac atria has recently been discovered. These peptide hormones have important functions in the regulation of blood volume and fluid homeostasis. We have measured plasma concentrations of atrial natriuretic peptides (ANP) in two patients during acute volume expansion. ANP concentrations increased in relation to an increase in right atrial pressure, and significant diuresis/natriuresis was observed. We conclude that hormonal as well as neuronal mechanisms are activated by acute volume loading in man.     

Muscle Water and Electrolytes in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis

ABSTRACT. Muscle water and electrolytes were determined in percutaneous muscle biopsy material from m. quadriceps femoris in 33 uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD) for 1–38 months, and in 34 normal subjects. The patients showed increased muscle contents of water, sodium, and chloride relative to fat-free solids (FFS); both intra- and extracellular water contents were increased. The total water content was inversely correlated with the duration of CAPD. The muscle potassium content was increased, both relative to FFS and to magnesium, whereas the intracellular potassium concentration was normal. Despite hypermagnesemia, the muscle content of magnesium was normal and the intracellular concentration was even slightly decreased due to the increase in intracellular water. We conclude that muscle water and electrolyte status is abnormal in CAPD patients, but the alterations appear to be less marked than in uremic patients undergoing other forms of therapy.     

Variability of Blood Pressure in Ambulatory Hypertensive Patients: Effects of Verapamil on Twice and Thrice Daily Dose Regimens

ABSTRACT The antihypertensive effects of verapamil over 24 hours were assessed on twice and thrice daily dose regimens on 12 patients (25–65 years of age; mean age 50) with essential hypertension (WHO stages I–II) in a randomised, double-blind, cross-over trial. After a dose titration period starting with either verapamil 80 mg tid or 120 mg bid the patients kept their maintenance dose (240, 360 or 480 mg daily) for 4 weeks before crossing over to the other administration schedule. Repeated ambulatory blood pressure (BP) curves were recorded in 10 patients with a non-invasive portable device (Pressurometer III, Del Mar Avionics). The BP reductions (causal BP values) obtained by 2- and 3-dose regimens were of similar magnitude (from 170±19/105±8 on placebo to 140±17/87±7 and to 146±14/88±8 by 2- and 3-dose respectively). Analyses of BP curves revealed close similarity in profiles on the two dose regimens, although DBP was significantly (p<0.05) lower by 3-dose as compared to 2-dose regimen during the period 0.00–2.59 a.m. Long-term (circadian rhythm) and short-term variability did not differ between the regimens. Despite the slight difference in DBP curves after midnight, the overall impression is that verapamil given both twice and thrice daily provides adequate BP control throughout 24 hours.     

Reduced High Density Lipoproteins as a Risk Factor after Acute Myocardial Infarction

ABSTRACT. FranzÉn J, Johansson BW, Gustafson A (Department of Internal Medicine, University Hospital, Lund and Section of Cardiology, Department of Internal Medicine, MalmÖ General Hospital, MalmÖ, Sweden). Reduced high density lipoproteins as a risk factor after acute myocardial infarction. In a group of normocholesterolemic, non-diabetic middle-aged males surviving an acute myocardial infarction for 4±2 years (mean ± SD), we have previously described a low apolipoprotein A-1 and a deficient fibrinolytic activity as two major characteristics. In the present study we have followed morbidity and mortality risk factors for five years in these males. Mortality was 40% in a hypertensive group and 16% in a normotensive group. In the normotensive group mortality was related to reinfarction. Furthermore, patients with a poor prognosis in the normotensive group had lower high density lipoprotein (HDL) cholesterol and lower apolipoprotein A-I concentration in plasma than patients with a good prognosis. Unexpectedly, in the hypertensive group death was related to a low (p<0.05) cortisol concentration in urine. It is concluded that a low HDL level may be a bad prognostic sign in males who have sustained an acute myocardial infarction and show no evidence of other risk factors, such as diabetes, hypercholesterolemia or hypertension.     

Effects of indomethacin on regional blood flow in conscious rabbits—a microsphere study

In an attempt to reveal the importance of prostaglandins in the control of regional blood flow 20 mg/kg b.wt. indomethacin was given i.v. in conscious resting rabbits. Regional blood flow determinations were made before and 20 min after the injection using the labelled microsphere technique. The blood flow in the stomach wall was reduced by 0.75 ± 0.17 g·min^-1·g^-1 from a level of 1.64 ± 0.24 g·min^-1·g^-1. In jejunum the corresponding figures were 0.44 ± 0.12 and 1.26 ± 0.17 and in the brain 0.29 ± 0.10 and 1.24 ± 0.10. The blood flow in the liver via the hepatic artery increased by 0.20 ± 0.02 g·min^-1·g^-1 from a level of 0.13 ± 0.02 g·min^-1·g^-1. In the retina there was a reduction in blood flow by 2.75 ± 1.03 mg·min^-1 from a starting level of 15.1 ± 2.3 mg·min^-1. In a number of other tissues investigated there were no significant effects of the drug. The results suggest that under resting conditions prostaglandins play a role in the control of blood flow in the gastrointestinal tract, the brain and the retina—tissues which are likely to be rather active under such conditions.     

Vasomotor effects of facial nerve stimulation: noncholinergic vasodilation in the eye

The effect of facial nerve stimulation on ocular blood flow was studied in rabbits. The intracranial part of the facial nerve was stimulated electrically and the regional blood flow was measured with labelled microspheres. Effects on the intraocular pressure were determined in a separate series of experiments. Stimulation increased choroidal blood flow by about 200%. The blood flow of the iris and the ciliary processes also increased. The blood flow of the eyelids and the nictitating membrane increased by approximately 1000%, and the blood flow of Harder's gland increased by about 200%. The blood flow of the tongue and the submandibular gland also increased. The increase in the uveal blood flow could not be abolished by a cholinergic or ganglionic blockade. Ganglionic blockade abolished most of the increase in the blood flow of the eyelids, nictitating membrane and Harder's gland; the cholinergic blockade seemed less effective. The intraocular pressure increased with a mean value of 6 mmHg during optimal (20–30 Hz) stimulation. The increase could not be prevented by cholinergic blockade. Much of the increase in uveal blood flow seemed to be caused by stimulation of unconventional nerves. It is suggested that these nerves may be peptidergic using VIP as a transmitter and lacking a hexamethonium sensitive synapse between the site of stimulation and the eye. Their nature—afferent or efferent—remains unknown. A great part of the increase in blood flow of the eyelids, nictitating membrane and Harder's gland seemed to be due to other mechanisms involving nerves with a peripheral synapse.     

Site-specific biotinylation

We have developed an expeditious method for the incorporation of the biotinylaminocaproyl moiety on the ε-amino group of a lysine residue within a peptide chain in a site-specific manner. Using t-Boc chemistry for the solid phase synthesis approach and a base labile, acid stable protecting group (Fmoc-) for the ε-amino group of the target lysine, we prepared fully protected resin bound peptides which are site-specifically biotinylated. Following HF cleavage, the uniquely biotinylated peptides were obtained in a high degree of purity. Using this approach, a number of biotinylaminocaproyllysyl derivatives of a monocyclic Endothelin-1 analog were prepared. Synthesis of selected bicyclic analogs of high affinity monocycles led to the preparation of the bicyclic [Nle⁷]ET-1 analog containing ε-biotinylaminocaproyllysine at position-9. This peptide, with K_d= 0.08 nM, has 1000-fold higher affinity for the ET_A receptor than the commercially available N_α-biotinylated Endothelin-1. The general utility of this biotinylation methodology was demonstrated by the synthesis of a site-specifically biotinylated PTH analog which contained several side chain functionalized amino acid residues in its sequence. The synthetic method reported here is convergent in that it allows the facile variation of the length of the spacer and also offers the potential to introduce in a site specific manner other groups such as affinity labels and fluorescent tags.     

Orthogonal solid-phase synthesis of a monobiotinylated analog of Neuropeptide Y

Analogs of Neuropeptide Y (NPY) were synthesized with conventional Boc/benzyl protective group strategy. Instead of Asn⁷ in the native scquence, Boc-Lys(Alloc)-OH was incorporated. At the end of the synthesis the Alloc group was selectively removed by palladium-catalyzed hydrostannolysis and biotin coupled to the e-amino group of Lys⁷. After cleavage and characterization with plasma desorption mass spectrometry the N^e-7-biotinyl-[Lys⁷]-NPY and the nonbiotinylated analog [Lys⁷]-NPY were investigated as ligands to the NPY receptor from rat cerebral cortex. Both analogs were found to be high affinity ligands to the NPY receptor and bound with essentially the same affinity as unmodified NPY.     

Prevalence and trends of cigarette smoking in different occupational groups: Results of the Minnesota Heart Survey 1980-1982 and 1985-1987

The association between smoking and occupational status is exploredusing data from the Minnesota Heart Survey. 7,381 currentlyemployed subjects were included in the study (2,949 from the1980–1982 survey and 4,432 from the 1985–1987 survey).In the first survey the prevalence of current smokers rangedfrom 23 (professional) to 57% (service occupations) in men andfrom 15 (artists and writers) to 59 (repair and craft occupations)in women. Educational level, age, race, and sex were importantpredictors of smoking status in a logistic regression analysisusing combined data from the two surveys; occupational statuswas significantly associated with smoking after controllingfor these covariables. Public health efforts should focus moreon preventing smoking in lower educational groups and in thoseoccupational groups that have the highest prevalence of smoking.