DISPARATE EXPRESSION OF THE AVP GENE IN SABRA HYPERTENSION-PRONE AND HYPERTENSION-RESISTANT RATS

We recently re-inbred the original colony of SBH-SBN rats, a model of salt-induced hypertension. In the course of phenotyping the new colony , SBH/y were found to excrete a lower urine flow with a higher urine o smolality than SBN/y. Thus disparate water handling between the substr ains, a phenotype characteristic of the original colony, was retained throughout the selection procedure and transmitted down the generation s to the new colony. As water handling is directly Linked to arginine vasopressin (AVP) and in view of potential linkage of this phenotype t o salt sensitivity or resistance in terms of the development of hypert ension, the AVP axis was further investigated in the new substrains. B asal plasma AVP levels were higher in SBH/y (2.86 +/- 0.22 pg/ml; n = 10) than in SBN/y (1.98 +/- 0.11 pg/ml; n = 10, P < 0.05). Water depri vation for 48 h increased plasma AVP levels severalfold in both substr ains to similar levels. Niravoline, a kappa receptor agonist that inhi bits central release of AVP, produced at 0.6 and 0.9 mg/kg a more prof ound diuretic effect in SBN/y than in SBH/y, suggesting greater pituit ary release of AVP into the circulation of SBH/y. AVP mRNA contents we re compared in SBH/y and SBN/y rats in whole hypothalamic extracts and in the supraoptic (SON) and paraventricular (PVN) nuclei by RNA prote ction assay. Under basal conditions, AVP mRNA content (in ng) in the h ypothalamus of SBH/y was 4.48 +/- 0.52 (n = 29) and of SBN/y was 3.13 +/- 0.35 (n = 30), P < 0.05; in the SON of SBH/y, AVP mRNA content was 3.62 +/- 0.44 (n = 11) and of SBN/y was 2.21 +/- 0.54 (n = 10), P < 0 .05; in the PVN of SBN/y, AVP mRNA content was 0.78 +/- 0.16 (n = 9) a nd of SBN/y was 0.77 +/- 0.13 (n = 11, not significant). Thus the diff erences in hypothalamic AVP mRNA were primarily in the SON. Water depr ivation as well as salt loading (8% NaCl) induced a significant elevat ion in AVP mRNA content in SBN/y but a blunted response in SBH/y. Thes e data suggest that there is genetically transmitted enhanced hypothal amic expression of the AVP gene in SBH/y compared with SBN/y which res ults, under basal conditions, in greater pituitary release of AVP, in higher plasma AVP levels, and in increased renal concentrating activit y. As AVP has been implicated in various forms of hypertension, these findings render AVP a candidate gene for salt sensitivity or resistanc e in the Sabra rat model of hypertension.