Development of a New Strain of Spontaneously Hypertensive Rats Homozygous for Hypothalamic Diabetes Insipidus

The aim of the present study was to investigate whether the presence of arginine vasopressin (AVP) is necessary for the establishment of high blood pressure in spontaneously hyper-tensive rats (SHR). For this purpose we crossbred SHR of the stroke-prone substrain (SHRSP) with rats homozygous for hypothalamic diabetes insipidus of the Brattleboro strain (DI) which are unable to synthetize AVP. The successful introduction of the DI gene into the SHRSP strain (SHRDI) was demonstrated by the following observations: In 10-month-old rats, water intake was similarly elevated in SHRDI as in DI rats (137 ± 6.5 vs 125 ± 10.5 ml per 24 hours). AVP was undetectable in the plasma, in the hypothalamus, and in the pituitary of SHRDI and DI rats. Urine osmolality and urinary concentration of sodium and potassium were markedly reduced. SHRDI and DI did not adequately concentrate their urine during an 8-hour period of water deprivation, but both strains of rats responded well with a fall in urine output and a rise in urine osmolality to subcutaneous administra-tion of the non-pressor analog of AVP, DDAVP. Mean arterial blood pressure was markedly increased in SHRDI as well as in SHRSP (184 ± 9.7 vs 197 ± 5.2 mm Hg). Thus, we have developed a new line of spontaneously hypertensive rats homozygous for hypothalamic diabetes insipidus. From this finding it is concluded that AVP is not essential for the development and maintenance of spontaneous hyperten-sion of rats.

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