Effect of angiotensin II in ventrolateral medulla of spontaneously hypertensive rats.
The spontaneously hypertensive rat (SHR) exhibits an enhanced activity of the peripheral sympathetic and brain renin-angiotensin systems. In the present experiments, we evaluated the cardiovascular response of angiotensin II (ANG II) microinjected in the rostral (RVLM) and the caudal (CVLM) ventrolateral medulla of age-matched (14-16 wk old) SHR and Wistar-Kyoto (WKY) rats. Responses of mean arterial pressure (MAP) and heart rate (HR) to microinjection of ANG II (5, 20 and 100 pmol) into histologically verified sites of the RVLM and CVLM were compared with those obtained by injections of the excitatory agent L-glutamate (2 nmol) at the same site. In both strains, ANG II elicited dose-dependent pressor responses in the RVLM and depressor responses in the CVLM, both of which peaked at a dose of 20 pmol. The magnitude of the fall in MAP produced by injections of ANG II into the CVLM were significantly (P less than 0.01) greater in SHR than in WKY group. In contrast, peak pressor responses elicited by injection of ANG II into the RVLM were of similar magnitude in the two groups. When compared with the MAP response produced by L-glutamate injections, responses to ANG II microinjection were slower in onset, and the latency to the peak response was longer. Ganglionic blockade with hexamethonium bromide prevented the effect of ANG II injection in the RVLM. This study provides evidence that ANG II acts as an excitatory agent at sites within the ventrolateral medulla that determine the vasomotor control of blood pressure in both normotensive and hypertensive rats.
Department of Brain and Vascular Research, Cleveland Clinic Foundation, Ohio 44195.
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H
Muratani
D B
DB
Averill
C M
CM
Ferrario
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005730:Ganglionic Blockers / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006439:Hemodynamics / Q000187:drug effects; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008526:Medulla Oblongata / Q000098:blood supply / Q000187:drug effects*; D008845:Microinjections; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011921:Rats, Inbred WKY
D005730:Ganglionic Blockers; D005971:Glutamates; D006584:Hexamethonium Compounds; D000804:Angiotensin II; D018738:Hexamethonium; D018698:Glutamic Acid