Rostral ventrolateral medulla neurons of neonatal Wistar-Kyoto and spontaneously hypertensive rats.
We compared the electrophysiological properties of neurons in the rostral ventrolateral medulla (RVLM) of neonatal Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), and responses to angiotensin II and its type 1 receptor antagonist candesartan. Using the whole-cell patch-clamp technique, we examined the characteristics of RVLM neurons in brainstem-spinal cord preparations with a preserved sympathetic neuronal network. The baseline membrane potential of irregularly firing neurons was less negative (-50.1+/-0.6 versus -52.0+/-0.6 mV) and the firing rate was faster (3.0+/-0.2 versus 2.0+/-0.2 Hz) in SHR (n=56) than in WKY (n=38). Superfusion with angiotensin II (6 micromol/L) significantly depolarized the RVLM bulbospinal neurons in SHR (5.4+/-1.1 mV, n=15) but not in WKY. In contrast, candesartan (0.12 micromol/L) induced a significant membrane hyperpolarization (-3.7+/-0.4 mV; n=14) and a decrease in the firing rate in RVLM bulbospinal neurons of SHR but not of WKY. These results suggest that endogenously generated angiotensin II binds to type 1 receptors on RVLM bulbospinal neurons, thus tonically contributing to a higher membrane potential and a faster firing rate in SHR. The electrophysiological properties of RVLM neurons and their responses to angiotensin II and candesartan differ between neonatal WKY and SHR. These differences in RVLM neurons suggest a mechanism that possibly leads to elevation in blood pressure.
D000200:Action Potentials; D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000831:Animals, Newborn; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001933:Brain Stem / Q000166:cytology / Q000503:physiopathology*; D002478:Cells, Cultured; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D013116:Spinal Cord / Q000166:cytology / Q000503:physiopathology*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000804:Angiotensin II; C081643:candesartan