Baroreflex modulation by angiotensins at the rat rostral and caudal ventrolateral medulla

Abstract

-We determined the effect of microinjection of ANG-(1-7) and ANG II into two key regions of the medulla that control the circulation [rostral and caudal ventrolateral medulla (RVLM and CVLM, respectively)] on baroreflex control of heart rate (HR) in anesthetized rats. Reflex bradycardia and tachycardia were induced by increases and decreases in mean arterial pressure produced by intravenous phenylephrine and sodium nitroprusside, respectively. The pressor effects of ANG-(1-7) and ANG II (25 pmol) after RVLM microinjection (11 Ϯ 0.8 and 10 Ϯ 2 mmHg, respectively) were not accompanied by consistent changes in HR. In addition, RVLM microinjection of these angiotensin peptides did not alter the bradycardic or tachycardic component of the baroreflex. CVLM microinjections of ANG-(1-7) and ANG II produced hypotension (Ϫ11 Ϯ 1.5 and Ϫ11 Ϯ 1.9 mmHg, respectively) that was similarly not accompanied by significant changes in HR. However, CVLM microinjections of angiotensins induced differential changes in the baroreflex control of HR. ANG-(1-7) attenuated the baroreflex bradycardia (0.26 Ϯ 0.06 ms/mmHg vs. 0.42 Ϯ 0.08 ms/mmHg before treatment) and facilitated the baroreflex tachycardia (0.86 Ϯ 0.19 ms/mmHg vs. 0.42 Ϯ 0.10 ms/mmHg before treatment); ANG II produced the opposite effect, attenuating baroreflex tachycardia (0.09 Ϯ 0.06 ms/mmHg vs. 0.31 Ϯ 0.07 ms/mmHg before treatment) and facilitating the baroreflex bradycardia (0.67 Ϯ 0.16 ms/mmHg vs. 0.41 Ϯ 0.05 ms/mmHg before treatment). The modulatory effect of ANG II and ANG-(1-7) on baroreflex sensitivity was completely abolished by peripheral administration of methylatropine. These results suggest that ANG II and ANG-(1-7) at the CVLM produce a differential modulation of the baroreflex control of HR, probably through distinct effects on the parasympathetic drive to the heart. baroreflex control of heart rate; renin-angiotensin system; arterial pressure THE BARORECEPTOR AFFERENTS terminate primarily in the intermediate portion of the nucleus of the solitary tract (NTS) subjacent to the area postrema in the dorsal medulla (15, 32). Although many brain stem and forebrain regions participate in the modulation of the sympathetic and parasympathetic outflows, regions inside the ventrolateral medulla (VLM) are essential for the effectiveness of the baroreceptor reflex (32). The caudal VLM (CVLM) has been functionally defined as a tonically active sympathoinhibitory vasodepressor region (15,32,44) that contains a synaptic relay within the baroreflex circuit, connecting the NTS to a site on the sympathoexcitatory reticulospinal neurons, the rostral VLM (RVLM). The RVLM is known to play an essential role in the tonic and reflex control of sympathetic vasomotor tone (15, 32). Two groups of cardiovascular neurons have been functionally defined in the CVLM: neurons that relay baroreflex inputs from the NTS to the RVLM and neurons that are insensitive to the baroreflex input (14, 44). In addition, the CVLM depressor response, in part, is associated with vagally mediated decrease in h...

Baro-excited neurons in the caudal ventrolateral medulla (CVLM) recorded using the whole-cell patch-clamp technique

“…These results indicate that the CVLM neurons, Whole-cell patch-clamp of baro-excited CVLM neurons N Oshima et al which form inhibitory synapses with the RVLM neurons, were activated by Ang-II. Muratani et al 26 and Alzamora et al 27 obtained similar results. As the baro-excited CVLM neurons formed synapses with the RVLM neurons, these previous results [25][26][27] support our present data.…”

“…Muratani et al 26 and Alzamora et al 27 obtained similar results. As the baro-excited CVLM neurons formed synapses with the RVLM neurons, these previous results [25][26][27] support our present data. However, the findings of their studies and ours do not answer the question as to whether Ang-II activates the baro-excited CVLM neurons directly.…”

“…However, the findings of their studies and ours do not answer the question as to whether Ang-II activates the baro-excited CVLM neurons directly. Considering the results of previous studies, [25][26][27] we cannot deny the possibility that Ang-II may have activated non-baroexcited CVLM neurons and that these neurons in turn sent synaptic activity to the baro-excited CVLM neurons.…”

Cardiovascular effect of angiotensin-(1–12) in the caudal ventrolateral medullary depressor area of the rat

“…The CVLM neurons involved in the baroreflex are GABA-containing neurons, and they project to the RVLM (16,17,25,34,37). The presence of AT 1 Rs has been reported in the CVLM, and microinjections of ANG II into the CVLM decrease blood pressure (BP) (3,8). Microinjections of ANG-(1-7) into the CVLM have been reported to elicit depressor responses (2).…”

“…Unlike ANG II, renin is not involved in the formation of ANG-(1-12) (15,40), prompting the suggestion that ANG-(1-12) may act as a renin-independent alternative substrate for the formation of ANG II in several organs (40). In the periphery, ANG-(1-12) may exert its actions via a rapid conversion to ANG II because pressor responses elicited by intravenous injections of ANG- (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) in the rat were blocked by prior injections of an ANG type 1 receptor (AT 1 R) antagonist (29). Because it is known that ANG I and ANG II can be converted into ANG-(1-7) (41), there is a possibility that ANG-(1-7) may be formed from ANG- (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) in the brain.…”