Effects of the peptide release inhibitor, octreotide, on daytime hypotension and on nocturnal hypertension in primary autonomic failure.
OBJECTIVE
To investigate the effects of the somatostatin analogue octreotide, which inhibits the release of various peptides, on 24-h ambulatory blood pressure profiles in subjects with primary (idiopathic) autonomic failure due to sympathetic denervation, and in particular to determine whether octreotide reduces daytime hypotension and whether it causes or accentuates nocturnal hypertension.


METHODS
Eighteen subjects with primary autonomic failure, confirmed by detailed physiological and biochemical autonomic tests, were studied in a randomized manner on two occasions, with and without octreotide treatment (1 mu g/kg body weight subcutaneously, twice a day at 0800 and 1800 h). Blood pressure was measured using the SpaceLabs 90207 system. This was connected at 0900 h with programmed recordings at 30-min intervals until 2300 h and at 60-min intervals until the next morning. There were additional subject-initiated recordings after 5 min each of lying, sitting and standing four times during the day, while sitting after lunch at noon and while standing following walking in the evening. Additional analyses included calculation of cumulative sum (cusum)-derived parameters and construction of cusum plots.


RESULTS
After octreotide treatment, the overall mean daytime systolic/diastolic blood pressure (mmHg) was raised (123 +/- 2/77 +/- 1 without treatment versus 128 +/- 2/79 +/- 1 with treatment). There was a reduction in postural (supine versus standing: from 96 +/- 3/62 +/- 3 without treatment to 106 +/- 5/67 +/- 4 with treatment), postprandial (107 +/- 3/65 +/- 2 to 122 +/- 5/75 +/- 4) and exertion-induced (96 +/- 5/61 +/- 5 to 113 +/- 6/71 +/- 5) hypotension. Symptoms of hypotension were reduced by octreotide. Nocturnal blood pressure was lower after octreotide (139 +/- 3/84 +/- 1 versus 129 +/- 3/78 +/- 2). Analyses with the cusum technique further demonstrated blood pressure recovery during the day, with a reduction in the magnitude of change at night after octreotide treatment.


CONCLUSIONS
In primary autonomic failure, 24-h ambulatory blood pressure profiles and cusum analyses indicate that octreotide has beneficial effects in reducing postural, postprandial and exertion-induced hypotension, without causing or increasing nocturnal hypertension.
Cardiovascular Medicine Unit, St. Mary's Hospital Medical School, University of London, UK.
M
M
Alam
G
G
Smith
K
K
Bleasdale-Barr
D V
DV
Pavitt
C J
CJ
Mathias
D000328:Adult; D017763:Autonomic Denervation / Q000009:adverse effects*; D018660:Blood Pressure Monitoring, Ambulatory; D002940:Circadian Rhythm / Q000502:physiology*; D015444:Exercise; D005260:Female; D006728:Hormones / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007022:Hypotension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use*; D010455:Peptides / Q000187:drug effects* / Q000378:metabolism; D011187:Posture
D006728:Hormones; D010455:Peptides; D015282:Octreotide