Age-related changes in opioid peptide concentrations in brain and pituitary of spontaneously hypertensive rats. Effect of antihypertensive drugs and comparison with deoxycorticosterone acetate and salt hypertension.

Abstract

The relationship of age-dependent changes in concentrations of various opioid peptides in the brain and pituitary to the development of hypertension was studied in the spontaneously hypertensive rat (SHR). Normotensive Wistar-Kyoto (WKY) and Sprague-Dawley rats served as controls. Opioids determined were dynorphin A (1-8) [DN-A(1-8)], beta-endorphin (BE) and Met-enkephalin (ME). Three approaches were used: (1) temporal correlations of opioid concentrations with the onset of hypertension in 4-, 8-, 12- and 16-week-old rats; (2) study of opioid changes when hypertension development was prevented with antihypertensive drugs and (3) determination of possible opioid peptide changes in another rat model of hypertension, the deoxycorticosterone acetate (DOCA) + salt model. Opioid peptide concentration differences (SHR/WKY) found were as follows. There were much lower DN-A(1-8) levels in the SHR hippocampus and hypothalamus at all ages studied. At 12 and 16 weeks, coincidently with the onset of hypertension, lower levels of BE were found in the anterior lobe of the pituitary, but there were higher BE and ME levels found in the neurointermediate lobe (NIL). Prevention of hypertension in SHR by 8 weeks of oral therapy with guanethidine and hydralazine reversed the BE and ME changes in the NIL but not in the anterior lobe. There were no brain or pituitary changes in opioid peptide concentrations associated with DOCA-salt hypertension. The results are interpreted as supporting a role for altered concentrations of brain and pituitary opioids in the genesis of SHR hypertension.