STRAIN-ASSOCIATED DIFFERENCES IN HYPOXIC CHEMOSENSITIVITY OF THE CAROTID-BODY IN RATS

Studies in humans indicate genetic effects on the ventilatory response to hypoxia, but the site of these effects is unknown. The present stu dy explores the question of whether there are genetically directed eff ects on the intrinsic hypoxic chemosensitivity of the carotid body. Th e approach was to study these responses in two inbred rat strains [spo ntaneously hypertensive rats (SHR) and Fischer 344 (F-344)] and to mea sure in vivo carotid chemosensitivity as the change in carotid sinus n erve (CSN) activity during progressive, isocapnic hypoxia and the isol ated, in vitro responses of excised superfused carotid bodies, loaded with. the fluorimetric indicator fura 2, measured as the cytosolic cal cium response to moderate hypoxia (P-O2 = 55 mmHg). CSN responses in F -344 rats (n = 12) were uniformly low, with a shape parameter A of 13. 8 +/- 6.59 (SE), whereas responses in SHR (n = 15) were sevenfold high er (108 +/- 24.1; P < 0.002) and showed greater variation. In vitro, i ntracellular calcium responses of superfused carotid bodies estimated from the fluorimetric ratio (340/380 nm) showed a. greater peak increa se during hypoxia in carotid bodies from SHR (140 +/- 4.7%) than from F-344 rats (114 6.0%; P < 0.01). Our results indicate strain-related d ifferences in hypoxic chemosensitivity that are intrinsic to the carot id body and that could mediate genetic effects on ventilatory responsi veness to hypoxia.