Acta Physiologica 2010; Volume 198, Supplement 677
Joint Meeting of the Scandinavian and German Physiological Societies
CONNEXIN 37 CONTRIBUTES TO RESTING ARTERIAL PRESSURE BUT IS NOT ESSENTIAL FOR RENAL AND SYSTEMIC AGONIST-INDUCED VASOMOTOR RESPONSES.
Abstract number: P-SUN-52
JUST1 A, WAGNER1 C, SIMON1 A, DAUTZENBERG1 M, KURTZ1 A
OBJECTIVE: Connexins 37, 40, and 43 are expressed in mesangial, smooth muscle, renin-producing, and endothelial cells of the juxtaglomerular apparatus (JGA) in the kidney. The most abundant connexin in the JGA, Cx40, contributes to pressure-dependent renin regulation and tubuloglomerular feedback, but not to agonist-induced renal vasomotor responses. The present work investigated the role of Cx37. METHODS: Arterial pressure (AP) and renal blood flow (RBF) were measured in anesthetized Cx37-deficient knockout mice (Cx37-ko, n=4) and wild-types from the same colony (wt, n=4) during baseline and in response to iv. bolus injections of norepinephrine (NE, 25 ng), angiotensin II (ANGII, 0.6 ng), and acetylcholine (ACH, 25 ng). RESULTS: AP was reduced in Cx37-ko (77±2 vs. 88±2 mmHg (ko vs. wt), p<0.05). Heart rate (534±27 vs. 544±51 bpm), RBF (1.7±0.3 vs. 1.8±0.1 ml/min), body weight (28±1 vs. 26±1 g) and kidney weight (170±12 vs. 177±12 mg) were not different. Pressor responses to NE (+31±8% vs. +28±7%), ANGII (+17±3 vs. +12±1%), and ACH (-43±1 vs. -29±9%) did not differ between Cx37-ko and wt. Responses of renal vascular resistance (RVR) were about half as strong in Cx37-ko as in wt (NE: +33±10 vs. +76±30, ANGII: +43±9 vs. +86±20, ACH: -17±5 vs. -35±3%). However, pressor and constrictor effects of nitric oxide synthase (NOS) inhibition (L-NAME 25 mg/kg, ko n=3, wt n=2) were similar in Cx37-ko and wt (AP +34±7% vs. +33±10%, RBF -52±1 vs. -45±3%) and during NOS-inhibition agonist-responses did not differ between genotypes (e.g. ANGII: RVR +254% vs. +198%, n=2 each). CONCLUSION: Cx37-ko animals are hypotensive but show normal agonist-induced systemic vasomotor responses to NE, ANGII, and ACH. The attenuation of vasomotor responses in the kidney is likely due to the hypotension below the level of RBF autoregulation, as it was absent at the elevated AP during NOS-inhibition.
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Acta Physiologica 2010; Volume 198, Supplement 677 :P-SUN-52