Substance P dilates epicardial coronary arteries and increases coronary blood flow in humans.
The effects of intracoronary infusions of substance P in conscious humans on epicardial vessel diameter and coronary sinus oxygen saturation were investigated in 13 patients who had angiographically normal coronary arteries. The dose of substance P ranged from 2.8 to 89.6 pmol/min, starting at 2.8 pmol/min and rising by doubling increments. All infusions were performed for 2-minute periods. Epicardial vessel diameter was measured by a computerized analysis system (CAAS) of the angiogram performed at the end of each infusion period. Coronary sinus oxygen saturation (CSO2) was measured continuously by a fiber-optic oximeter catheter in the coronary sinus. A reduction of arterial pressure, indicative of a systemic effect of substance P, occurred only when infusions were 44.8 pmol/min or more. At considerably smaller dosages, a dose-dependent increase in the left anterior descending artery diameter was seen with substance P; maximal dilation occurred at a dosage of 11.2 pmol/min. The percent increase in vessel diameter for this dosage was 29.4 +/- 19.8% (mean +/- SD) at the distal site of analysis and 16.7 +/- 10% at the proximal site of analysis. CSO2 rose in a dose-dependent manner and was maximal at a dosage of 11.2 pmol/min, which caused a 14.6 +/- 7.2% O2 rise above the preinfusion saturation of 43.5 +/- 11.1% O2. As the heart rate-blood pressure double product showed no change, it is argued that these changes in CSO2 probably reflect rises in coronary flow that were seen with dosages of substance P without systemic effect. In three patients, preconstriction induced by ergonovine was reversed by substance P infusions, which produced a degree of dilation equivalent to that of isosorbide dinitrate. We conclude that substance P at very small dosages, which are without peripheral effects, causes in vivo epicardial coronary artery dilatation as well as resistive vessel dilatation in humans.
Crossman
D C
DC
Division of Cardiovascular Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Larkin
S W
SW
Fuller
R W
RW
Davies
G J
GJ
Maseri
A
A
D000328:Adult; D000368:Aged; D002637:Chest Pain / Q000175:diagnosis / Q000503:physiopathology; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004874:Ergonovine / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007472:Iohexol; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects; D013373:Substance P / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D013373:Substance P; D007472:Iohexol; D004874:Ergonovine