Structure of the heme-regulated eukaryotic initiation factor 2 alpha kinase. End group analysis and phosphoaminoacid content

The Mr 80,000 subunit of the inhibitor of protein synthesis that is activated in heme deficiency was purified from SDS gels. Radiolabelled reagents were used to determine the end terminal residues: the N-terminal residue was found to be only glutamine, and the C-terminal residue only valine. Phosphoaminoacids determination revealed both phosphoserine and phosphothreonine.     

Beta-adrenoceptors and the regulation of blood pressure and plasma renin during exercise

The relative role of beta 1- and beta 2-adrenoceptors in the regulation of blood pressure and plasma renin at rest and during exercise was studied in 17 normal male volunteers. They performed, in a randomized order and according to a double-blind crossover study design, three graded and uninterrupted exercise tests until exhaustion after being pretreated during 3 consecutive days with a placebo, with a predominantly beta 1-blocker (atenolol, 50 mg once/day), or with a predominantly beta 2-blocker (ICI 118551, 20 mg 3 times/day). Both drugs caused a decrease of heart rate, but the reduction by ICI 118551 was less pronounced at rest and no additional decline occurred at exercise. ICI 118551 did not affect blood pressure at rest, but during exercise diastolic blood pressure was higher than after a placebo. Atenolol lowered systolic blood pressure at rest and suppressed the exercise-induced increase in systolic blood pressure. At rest and during exercise plasma renin activity was lowered by predominantly beta 1-blockade and unchanged during beta 2-antagonism. The exercise-induced increase in plasma renin was, however, not affected by the beta 1-blocker. After atenolol the urinary excretion of aldosterone was decreased but the plasma aldosterone concentration was not changed. ICI 118551 did not alter plasma or urinary aldosterone. Our results therefore provide further evidence that the adrenoceptors mediating the release of renin at rest and during exercise in humans are partially of the beta 1-subtype, whereas beta 2-adrenergic receptors probably play only a minor role in the control of renin secretion, especially at exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between plasma renin activity and physical fitness in normal subjects

The relationship between plasma renin activity (PRA) at rest and physical fitness was studied in 40 normal young subjects on a liberal sodium intake. Plasma renin activity was measured in arterial blood withdrawn at the end of a 30-min period of rest in recumbency, while physical fitness was expressed by the highest oxygen uptake achieved during an uninterrupted graded exercise test performed in the sitting position on an electromagnetically braked ergometer bicycle (peak VO2). Log PRA correlated significantly and inversely with peak VO2 adjusted for body weight (r = -0.34; P less than 0.05) in single regression analysis. Using multiple regression and adjusted peak VO2, age, urinary sodium excretion and mean intra-arterial pressure as independent variables, no combination of two or more independent variables yielded significant partial correlation coefficients with log PRA. This correlation suggests that PRA at rest is inversely related to the subject's physical fitness.     

Effects of angiotensin II on arterial pressure, renin and aldosterone during exercise

To evaluate the effect of isotonic exercise on the response to angiotensin II, angiotensin II in saline solution was infused intravenously (7.5 ng X kg-1 X min-1) in seven normal sodium replete male volunteers before, during and after a graded uninterrupted exercise test on the bicycle ergometer until exhaustion. The subjects performed a similar exercise test on another day under randomized conditions when saline solution only was infused. At rest in recumbency angiotensin II infusion increased plasma angiotensin II from 17 to 162 pg X ml-1 (P less than 0.001). When the tests with and without angiotensin II are compared, the difference in plasma angiotensin II throughout the experiment ranged from 86 to 145 pg X ml-1. The difference in mean intra-arterial pressure averaged 17 mmHg at recumbent rest, 12 mmHg in the sitting position, 9 mmHg at 10% of peak work rate and declined progressively throughout the exercise test to become non-significant at the higher levels of activity. Plasma renin activity rose with increasing levels of activity but angiotensin II significantly reduced the increase. Plasma aldosterone, only measured at rest and at peak exercise, was higher during angiotensin II infusion; the difference in plasma aldosterone was significant at rest, but not at peak exercise. In conclusion, the exercise-induced elevation of angiotensin II does not appear to be an important factor in the increase of blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Carotid baroreflex sensitivity at rest and during exercise is not influenced by opioid receptor antagonism

Physical effort involves, along with an increase in the plasma concentration of beta-endorphin, profound cardiovascular adaptations. The aim of the present study was to investigate with the use of the variable neck chamber technique, the influence of the endogenous opioids on the carotid baroreflex control of blood pressure and heart rate at rest as well as during exercise. Ten normal volunteers exercised in the supine position up to 33% and 66% of their maximal exercise capacity and received, in a randomized double-blind cross-over protocol, either saline or naloxone (10 mg intravenously, followed by a continuous infusion of 10 mg.h-1). During exercise a progressive attenuation of the carotid baroreceptor reflex control of blood pressure and heart rate was noted. However, neither at rest nor during exercise, did opioid antagonism influence the carotid baroreceptor control of blood pressure and heart rate. Intra-arterial pressure and heart rate also remained unaffected. In contrast, both at rest and during exercise, naloxone administration produced a significant increase in the plasma concentration of cortisol. The latter suggests that in vivo the opioid receptors were effectively antagonized. In conclusion the present study confirms that opioids play only a minor role in cardiovascular homeostasis at rest. In addition, this study demonstrates that they are not involved in the cardiovascular adaptation to exercise, nor in the exercise-related attenuation of the carotid baroreceptor control of pressure and heart rate.