Protein kinase C activation-induced increases of neural activity are enhanced in the hypothalamus of spontaneously hypertensive rats.

We have previously reported that some neurons in the anterior hypothalamic area (AHA) are tonically activated by endogenous angiotensins in rats and that activities of these angiotensin II-sensitive neurons in the AHA are enhanced in spontaneously hypertensive rats (SHR). In addition, neural activations induced by both angiotensin II and glutamate were enhanced in the AHA of SHR. In this study, we examined whether intracellular neural activation mechanisms via protein kinase C (PKC) and a potassium channel are altered in angiotensin II-sensitive neurons in the AHA of SHR. Male 15- to 16-week-old SHR and age-matched Wistar-Kyoto rats (WKY) and Wistar rats were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Pressure application of the PKC activator phorbol 12-myristate 13-acetate (PMA) onto angiotensin II-sensitive neurons in the AHA of Wistar rats increased their firing rate. The increase of unit activity by PMA was inhibited by the potent inhibitor of PKC, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), but not by the weak PKC inhibitor, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide hydrochloride (HA1004). The increase of unit firing by PMA was enhanced in SHR as compared with WKY. Pressure application of H-7 alone decreased the basal firing activity of angiotensin II-sensitive neurons in SHR but not in WKY. HA1004 did not affect the basal firing activity of angiotensin II-sensitive neurons in SHR. Angiotensin II-induced increases of firing rate in AHA neurons were inhibited by H-7 and the inhibition by H-7 was enhanced in SHR as compared with WKY. Pressure application of 4-aminopyridine, a blocker of the transient potassium current, onto angiotensin II-sensitive neurons increased their firing rate and the increase of unit firing rate was almost the same in WKY and SHR. These findings indicate that activation of PKC increases neural activity in angiotensin II-sensitive neurons in the AHA and that this PKC activation-induced increase of neural activity is enhanced in the AHA of SHR. It seems likely that the enhanced PKC activation effect is responsible for the enhanced basal neural activity seen in the AHA of SHR.