Effects of octreotide on cardiovascular hormones and haemodynamics in conscious dogs

Abstract

Octreotide inhibits the secretion of several hormones and exerts vasopressor effects. To clarify the mechanism of atrial natriuretic factor (ANF) secretion and to assess the cardiovascular effects of octreotide in relation to changes in vasoactive peptide secretion, four groups of conscious dogs were studied: group I (n = 11) received saline infusion after placebo, group II (n = 10), the same infusion after octreotide, group III (n = 10), placebo only and group IV (n = 10) octreotide injection only. Saline (10% body wt) was infused over 40 min after subcutaneous injection of placebo or octreotide (1 microgram/kg). Saline produced a rise (p < 0.001) of plasma ANF from 32.4 +/- 4.1 to 59.0 +/- 8.5 pM after placebo and from 35.6 +/- 5.5 to 77.0 +/- 12.6 pM after octreotide. This rise, not significantly different between groups I and II paralleled a 4-5-fold increase (p < 0.005) of right and left atrial pressures. With a higher dose of octreotide (4 micrograms/kg) injected in 4 dogs, plasma ANF increased by 27.5 +/- 5 pM. During hypervolemia, plasma endothelin-1 remained unchanged but plasma angiotensin II and epinephrine decreased (p < 0.05) approximately by 80% without being affected by octreotide. Octreotide did not influence the basal secretion of ANF, endothelin-1, angiotensin II and catecholamines. However, in basal conditions, octreotide injection resulted in a 9% increase (p < 0.005) of left ventricular systolic pressure, unobserved after placebo. Plasma glucose decreased (p < 0.005) in groups receiving octreotide. Thus, octreotide does not impair the stretch-mediated release of ANF which implies a release mechanism independent from somatostatin receptors and consequent changes in intracellular c-AMP. Octreotide has also a pressor effect, unrelated to changes in vasoactive peptide production.

Effects of Different Octreotide Dosages on Splanchnic Hemodynamics and Glucagon in Healthy Volunteers

“…Among insulin [15], VIP [16], substance P [17]and others, glucagon has a vasodilative effect on the mesenteric vascular bed and has been proposed as one regulator of mesenteric and portal blood flow [18, 19, 20]. The release of glucagon from the pancreatic α-cell is under the inhibitory control of somatostatin and its analogues [18, 21]. However, few studies have systematically compared the glucagon levels with the hemodynamic effects of octreotide.…”

Long‐term haemodynamic effects of octreotide on postprandial splanchnic hyperemia in humans: a placebo‐controlled echo–doppler study

“…As discussed above, a direct vascular action as well as suppression of gastrointestinal hormones such as glucagon are not the major mechanism involved. In this context it might be of interest to measure secretion of catecholamines, which are not influenced by octreotide under basal conditions in conscious dogs, 44 but which rose after an insulin‐induced hypoglycemia in normal subjects, parallel with superior mesenteric artery flow 45 . Possibly, stimulation of different somatostatin receptor subtypes 46 together with hormone interactions may explain the divergent vascular actions on basal and stimulated splanchnic flow following octreotide.…”