Intracoronary PGE2 and veratrine inhibits renin release in conscious dogs via chemosensitive ventricular afferents.
1. Prostaglandins (PG) and veratrum alkaloids stimulate ventricular sensory receptors with non-myelinated vagal afferents and mediate inhibitory circulatory responses. 2. The present study in conscious instrumented dogs was carried out to determine the effects of intracoronary artery infusions of veratrine (Ver-IC) and PGE2 (PGE2-IC) on plasma renin activity (PRA). 3. A 15-20 mmHg decrease in arterial pressure was produced during Ver-IC (0.2-0.8 micrograms/kg per min) and PGE2-IC (10-50 ng/kg per min), but there was no change in PRA or heart rate. 4. In contrast, significant increases in PRA (+3.51 +/- 0.37 ng angiotensin I/mL per h; P less than 0.01) and heart rate (+38.5 +/- 6.2 beats/min; P less than 0.001) were elicited in response to a 15-20 mmHg decrease in arterial pressure produced by intravenous infusions of nitroprusside. 5. Pharmacological blockade of afferent fibres in the pericoronary region of the left main coronary artery during Ver-IC resulted in significant hypotension-induced increases in PRA (P less than 0.001) and heart rate (P less than 0.001), thus removing the inhibitory influence of chemosensitive ventricular afferents. 6. Therefore, intracoronary veratrum alkaloids and prostaglandins inhibit hypotension-induced increases in PRA and heart rate in the conscious dog. This is mediated by chemosensitive receptors located in the left ventricular myocardium along with afferent nerves in the pericoronary region and cervical vagi.
Gorman
A J
AJ
Department of Biological Research, Hoechst-Roussel Pharmaceuticals Inc., Somerville, New Jersey 08876.
Chen
J S
JS
Foster
S
S
Snyder
R G
RG
Iams
S G
SG
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003331:Coronary Vessels; D015232:Dinoprostone / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000294:innervation*; D007261:Infusions, Intra-Arterial; D008297:Male; D009407:Nerve Block; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D011863:Radioimmunoassay; D012083:Renin / Q000097:blood*; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000502:physiology; D014702:Veratrine / Q000494:pharmacology*
D009599:Nitroprusside; D012083:Renin; D014702:Veratrine; D015232:Dinoprostone