Birgitta Linde

Sympatho-adrenal and cardiovascular reactivity in pregnancy-induced hypertension. I. Responses to isometric exercise and a cold pressor test

Summary. Sympatho‐adrenal and cardiovascular reactivity was studied in patients with pregnancy‐induced hypertension (PIH) and healthy pregnant controls subjected to an isometric handgrip test and a cold pressor test both during and after the pregnancy. At rest, heart rate was higher in the PIH group than in the control group both during and after pregnancy. Forearm vascular resistance was not affected by PIH or by pregnancy per se. During pregnancy arterial plasma adrenaline levels were suppressed in the control group both when compared with the PIH group and postpartum values. Arterial noradrenaline levels were similar and normal in the two groups at both examinations. The iso‐metric exercise increased systolic and diastolic blood pressures, heart rate and noradrenaline and reduced vascular resistance similarly in the PIH and control groups on both occasions. Vasoconstrictor responses to the cold pressor test were reduced during prenancy but there were no differences between the groups on either occasion. Noradrenaline responses to the cold pressor test were not influenced by PIH or by pregnancy per se. During pregnancy adrenaline responses to the two tests tended to be reduced in the controls but not in PIH. Our results indicate enhanced adrenomedullary activity in PIH when compared with the suppressed activity in normal pregnancy. Cardiovascular reactivity to the tests was similar in the PIH and control groups. The normal arterial noradrenaline levels at rest and during provocation do not support the contention of a generalized increase in sympathetic nerve activity in PIH

Sympathoadrenal and cardiovascular reactivity in pregnancy-induced hypertension: II. Responses to tilting☆

Sympathoadrenal and cardiovascular responses to tilting were studied in patients with pregnancy-induced hypertension and healthy control subjects during the last trimester of pregnancy and 8 to 12 weeks post partum. Blood volumes were lower in the patients with pregnancy-induced hypertension during pregnancy (0.065 versus 0.081 L/kg, p less than 0.01) but not post partum. Tilting induced significantly smaller increases in heart rate and arterial plasma norepinephrine concentrations and smaller changes in blood pressure during pregnancy as compared to after pregnancy in both groups. Forearm vascular resistance increased significantly in both groups after pregnancy but only in the patients with pregnancy-induced hypertension during pregnancy. The forearm vasoconstrictor response to tilting was, in fact, totally abolished in the third trimester of normal pregnancy. The hypertensive patients had higher arterial plasma epinephrine levels at rest and greater epinephrine and norepinephrine responses to tilting than the control subjects during pregnancy. Normal pregnancy appears to reduce the circulatory and sympathoadrenal responses to orthostatic stress, presumably because of volume expansion that allows venous return to be better maintained in the upright position. The less pronounced pregnancy-induced increase in blood volume in patients with pregnancy-induced hypertension appears to explain the increased sympathoadrenal and forearm vascular reactivity in this group during pregnancy.

Absorption of Rapid-Acting Insulin in Obese and Nonobese NIDDM Patients

OBJECTIVE To study the absorption rate of rapid-acting insulin from subcutaneous injection sites in nonobese and obese non-insulin-dependent diabetes mellitus (NIDDM) patients. RESEARCH DESIGN AND METHODS Ten nonobese and 10 obese NIDDM patients (body mass indexes 24.1 ± 0.4 and 31.4 ± 0.8 kg/m2, respectively) received four subcutaneous injections of 125I-labeled rapid-acting insulin (Actrapid Human, 5 U): three in the abdominal wall above, lateral to, and below the umbilicus; and one in the thigh. The depth of the subcutaneous fat layer was measured using ultrasound techniques. The residual radioactivity was monitored externally for 270 min. RESULTS The disappearance half-life of 125I-insulin was between 4 and 6 h from all injection sites, with the exception of the upper abdominal area in the nonobese subjects, where it measured ∼ 3 h. The residual radioactivity did not differ between nonobese and obese patients measured from any of the sites. In the nonobese group, the most rapid absorption of 125I-insulin was found from the upper abdominal area and the slowest from the thigh. In the obese group, the absorption rates did not differ between sites. No correlation was found between the depth of the fat layer and the residual radioactivity when measured at any site. CONCLUSIONS Our results indicate that the absorption of rapid-acting insulin is markedly slow in both obese and nonobese NIDDM patients compared with IDDM patients and healthy subjects studied previously. In the nonobese group, the most rapid absorption of 125I-insulin is obtained after injection into the upper abdominal area. Inter- and intraregional differences are small in the obese patients. Consequently the choice of injection site is of little importance in this group.

Influence of Circulating Epinephrine on Absorption of Subcutaneously Injected Insulin

Effects of epinephrine (Epi) infusion on the absorption of subcutaneously injected 125I-labeled soluble human insulin (10 U) from the thigh or the abdomen were studied in 16 healthy subjects and from the thigh in 10 insulin-dependent diabetic (IDDM) patients. Epi was infused at 0.3 (high dose) or 0.1 (low dose; healthy subjects) nmol · kg−1 · min−1 i.v., resulting in arterial plasma Epi levels of ∼6 and 2 nM, respectively. Saline was infused on a control day. Insulin absorption was measured as disappearance of radioactivity from the injection site and as appearance of plasma immunoreactive insulin (IRI). Adipose tissue blood flow was measured with the 133Xe clearance technique. First-order disappearance rate constants of 125I from the thigh depot decreased ∼40–50% during the high dose of Epi compared with control (P < .001). The corresponding decrease from the abdominal depot was ∼40% (P < .001), whereas no significant change was found during the low Epi dose. IRI fell compared with control in all groups at the high Epi dose. The Epi-induced depression of insulin absorption occurred despite unaltered or even slightly increased subcutaneous blood flow. The results indicate that circulating Epi at levels seen during moderate physical stress depresses the absorption of soluble insulin from subcutaneous injection sites to an extent that might be important for glycemic control in IDDM patients. Furthermore, dissociation is found between changes in insulin absorption and subcutaneous blood flow during Epi infusion, suggesting that factors other than blood flow may also influence the absorption of subcutaneously injected insulin.

Insulin Absorption, Glucose Homeostasis, and Lipolysis in IDDM During Mental Stress

Objective To study the effects of mental stress on the absorption kinetics of insulin and on glucose homeostasis and lipolysis in insulin-dependent diabetes mellitus (IDDM). Research Design and Methods Nine IDDM patients were exposed to the Stroop color word conflict test (CWT) during 40 min after injection of 125I-labeled soluble human insulin (10 U) into the abdomen. Adipose tissue blood flow (133Xe-clearance) was determined concomitantly to elucidate the importance of blood flow for insulin absorption during CWT. The effect of the CWT was followed by measurement of arterial levels of catecholamines and as blood pressure and heart-rate responses. Lipolysis was measured as arterial glycerol levels, and ketone body levels were monitored by determination by β-hydroxybutyrate. Results Although insulin absorption (residual 125I-radioactivity and plasma free insulin levels) and the arterial levels of glucose and β-hydroxybutyrate were not significantly changed by the CWT, arterial glycerol and norepinephrine levels and adipose tissue blood flow were ~ doubled, and epinephrine levels increased fourfold. Heart rate increased ~ 35 beats/min and mean blood pressure ~ 25 mmHg. Conclusions The results suggest that intense mental stress of 40 min duration does not alter the absorption of subcutaneously injected insulin, glucose homeostasis, or ketone body levels in patients with IDDM, despite a considerable increase in blood flow and lipolysis.

Sympatho-adrenal regulation of adipose tissue blood flow in dog and man

1. A comparison is made between the sympatho-adrenal regulation of subcutaneous adipose tissue blood flow in the dog and in man. 2. In the dog neuronally released noradrenaline causes vasoconstriction in subcutaneous adipose tissue by preferential activation of alpha-adrenoceptors located close to the sympathetic nerve terminals. 3. In man sympathetic reflex activation also causes vasoconstriction in subcutaneous adipose tissue, presumably via activation of alpha-adrenoceptors. 4. The adipose tissue vascular beta-adrenoceptors are of the beta 1-subtype in the dog and the beta 2-subtype in man. 5. Because of this adrenaline causes vasoconstriction in dog adipose tissue and vasodilation in human adipose tissue.