Altered neuropeptide concentrations in spontaneously hypertensive rats: cause or consequence?

Changes in brain neuropeptide content in spontaneously hypertensive rats may be primarily related to the development of hypertension or may be secondary consequences of it. We have measured brain concentrations of beta-endorphin, Leu-enkephalin, arginine vasopressin (AVP) and oxytocin (OXT) in stroke-prone spontaneously hypertensive rats (SHRSP) and in age-matched normotensive Wistar Kyoto (WKY) controls, as well as in SHRSP with normalized blood pressure by chronic treatment with clonidine. Opioid peptide contents were measured in 12-, 18- and 24-week-old rats. beta-Endorphin was measured in the neuro-intermediate and anterior lobes of the pituitary, the hypothalamus, mid-brain and brain stem; Leu-enkephalin in the neuro-intermediate lobe of the pituitary, hypothalamus, mid-brain, brain stem, as well as in the spinal cord and adrenal glands. AVP and OXT were measured in the neuro-intermediate lobe of the pituitary, hypothalamus, brain stem and spinal cord. beta-Endorphin in the neuro-intermediate lobe of the pituitary was significantly higher in 12- and 18-week-old SHRSP. Adrenal gland Leu-enkephalin was lower in SHRSP as compared with the WKY. OXT and AVP contents were markedly reduced in all brain regions of SHRSP except the neuro-intermediate lobe of the pituitary, where no significant changes were found. In no case did long-term antihypertensive treatment with clonidine reverse the altered peptide content in the SHRSP. We conclude that alterations in brain neuropeptide content in SHRSP are not secondary to hypertension. The blood pressure lowering activity of clonidine appears not to depend on major alterations of peptide concentrations. A genetic defect in the synthesis of adrenal enkephalins and hypothalamic OXT and AVP seems likely from these studies.