Central ventilatory and cardiovascular actions of angiotensin peptides in trout

Abstract

In the brains of teleosts, angiotensin II (ANG II), one of the main effector peptides of the renin-angiotensin system, is implicated in various physiological functions notably body fluid and electrolyte homeostasis and cardiovascular regulation, but nothing is known regarding the potential action of ANG II and other angiotensin derivatives on ventilation. Consequently, the goal of the present study was to determine possible ventilatory and cardiovascular effects of intracerebroventricular injection of picomole doses (5-100 pmol) of trout [Asn(1)]-ANG II, [Asp(1)]-ANG II, ANG III, ANG IV, and ANG 1-7 into the third ventricle of unanesthetized trout. The central actions of these peptides were also compared with their ventilatory and cardiovascular actions when injected peripherally. Finally, we examined the presence of [Asn(1)]-ANG II, [Asp(1)]-ANG II, ANG III, and ANG IV in the brain and plasma using radioimmunoassay coupled with high-performance liquid chromatography. After intracerebroventricular injection, [Asn(1)]-ANG II and [Asp(1)]-ANG II two ANG IIs, elevated the total ventilation through a selective stimulatory action on the ventilation amplitude. However, the hyperventilatory effect of [Asn(1)]-ANG II was threefold higher than the effect of [Asp(1)]-ANG II at the 50-pmol dose. ANG III, ANG IV, and ANG 1-7 were without effect. In addition, ANG IIs and ANG III increased dorsal aortic blood pressure (P(DA)) and heart rate (HR). After intra-arterial injections, none of the ANG II peptides affected the ventilation but [Asn(1)]-ANG II, [Asp(1)]-ANG II, and ANG III elevated P(DA) (50 pmol: +80%, +58% and +48%, respectively) without significant decrease in HR. In brain tissue, comparable amounts of [Asn(1)]-ANG II and [Asp(1)]-ANG II were detected (ca. 40 fmol/mg brain tissue), but ANG III was not detected, and the amount of ANG IV was about eightfold lower than the content of the ANG IIs. In plasma, ANG IIs were also the major angiotensins (ca. 110 fmol/ml plasma), while significant but lower amounts of ANG III and ANG IV were present in plasma. In conclusion, our study suggests that the two ANG II isoforms produced within the brain may act as a neurotransmitter and/or neuromodulator to regulate the cardioventilatory functions in trout. In the periphery, two ANG IIs and their COOH-terminal peptides may act as a circulating hormone preferentially involved in cardiovascular regulations.

Other Angiotensins

“…Intra-arterial injection of Ang III or Ang IV increases blood pressure in teleosts but Ang III has a higher potency than Ang IV. Intracerebroventricular (ICV) injection of Ang III increases the heart rate without affecting the blood pressure and ventilation rate in trout, in contrast to the effect of Ang II, which increases all three parameters [3]. ICV injection of Ang IV does not affect blood pressure, heart rate, and ventilation rate even though it is detected in the brain by immunoassays.…”

“…In eels, plasma Ang III and Ang IV are present in plasma but their levels are low compared to Ang II (Table 29C.2) [2]. In trout brain, Ang III is not detectable but Ang IV is present [3].…”

Brain neuropeptides in central ventilatory and cardiovascular regulation in trout

“…In contrast to the well known peripheral cardiovascular and osmoregulatory hormonal actions of Ang II (Olson, 1992; Le Mével et al, 1993; Bernier et al, 1999b; Takei and Balment, 2009), studies in fish on the central action of Ang II are sparse. Furthermore, two Ang II isoforms [Asn 1 ]- and [Asp 1 ]-Ang are present in plasma and tissues (Conlon et al, 1996; Wong and Takei, 2012) but the physiological roles of the latter form have only been recently explored (Lancien et al, 2012). Central administration of [Asn 1 ]-Ang II into the third or fourth ventricle of the eel Anguilla japonica induces drinking (Kozaka et al, 2003) and increases HR and blood pressure (Nobata et al, 2011).…”

“…Taken together, these results demonstrate that in the brains of teleosts, as in mammals, Ang II may act as a neuromodulator or a neurotransmitter involved in key osmoregulatory and cardiovascular regulations. Recently, the cardio-ventilatory actions of exogenously administered [Asn 1 ]-Ang II, [Asp 1 ]-Ang II, Ang III, Ang IV, and Ang 1–7 within the third ventricle of the trout brain have been described (Lancien et al, 2012). In addition, the angiotensin peptides produced in the brain and circulating in plasma of trout were characterized using a high performance liquid chromatography (HPLC) system that can separate these peptides (Lancien et al, 2012; Wong and Takei, 2012).…”

Hollow-layered nanoparticles for therapeutic delivery of peptide prepared using electrospraying

“…The technique used for placement of the electrocardiographic electrodes, recording of the ventilation, cannulation of the dorsal aorta, intra-arterial (IA) injection of the peptide, and data acquisition and analysis of the cardiovascular variables have been described previously in detail[35,36]. The ventilation signal was only used here to monitor the recovery of normal baseline ventilation after surgery and no quantification of the ventilatory variables was performed.…”