Cardiovascular actions of rattlesnake bradykinin ([Val¹,Thr⁶]bradykinin) in the anesthetized South American rattlesnakeCrotalus durissus terrificus

Abstract

actions of rattlesnake bradykinin ([Val 1 ,Thr 6 ]bradykinin) in the anesthetized South American rattlesnake Crotalus durissus terrificus. Am J Physiol Regul Integr Comp Physiol 288: R456 -R465, 2005. First published October 21, 2004; doi:10.1152/ajpregu.00417.2004.-Incubation of heat-denatured plasma from the rattlesnake Crotalus atrox with trypsin generated a bradykinin (BK) that contained two amino acid substitutions (Arg 1 3 Val and Ser 6 3 Thr) compared with mammalian BK. Bolus intra-arterial injections of synthetic rattlesnake BK (0.01-10 nmol/kg) into the anesthetized rattlesnake, Crotalus durissus terrificus, produced a pronounced and concentration-dependent increase in systemic vascular conductance (Gsys). This caused a fall in systemic arterial blood pressure (Psys) and an increase in blood flow. Heart rate and stroke volume also increased. This primary response was followed by a significant rise in Psys and pronounced tachycardia (secondary response). Pretreatment with N G -nitro-L-arginine methyl ester reduced the NK-induced systemic vasodilatation, indicating that the effect is mediated through increased NO synthesis. The tachycardia associated with the late primary and secondary response to BK was abolished with propranolol and the systemic vasodilatation produced in the primary phase was also significantly attenuated by pretreatment, indicating that the responses are caused, at least in part, by release of cathecholamines and subsequent stimulation of ␤-adrenergic receptors. In contrast, the pulmonary circulation was relatively unresponsive to BK.reptile; vasoactive kinin; catecholamines; nitric oxide; adrenergic receptor BRADYKININ (BK) is a peptide produced in the blood in response to tissue injury that exerts pronounced cardiovascular effects in all animals studied. These effects may contribute to regulation of local blood perfusion of damaged tissue and be involved in the paracrine regulation of organ perfusion (6). The effects of BK in mammals are mediated through the interaction with two well-characterized receptors, termed B1 and B2 (17). BK acts directly with receptors on smooth muscle to cause vasodilatation of the systemic vasculature. At higher doses, this response is rapidly followed by a rise in systemic pressure (Psys) above resting levels as heart rate and cardiac output increase (reviewed in 25). In reptiles, infusion of the species-specific BK consistently causes a systemic vasodilatation, but the changes in blood pressure and heart rate vary among species. In anesthetized alligators, Alligator mississipiensis, Psys decreased after injection of BK, but there was no secondary hypertensive response or increased heart rate (4). Turtles, Trachemys scripta, also exhibited a systemic vasodilatation after injection of BK, which was accompanied by an increased systemic blood flow (Qsys), while Psys remained constant. However, unlike mammals, turtles do not exhibit a tachycardia (8). In the python, Python regius, Psys increased after injection of python BK, despite a systemic vasodilat...

Hypoxic pulmonary vasoconstriction in reptiles: a comparative study of four species with different lung structures and pulmonary blood pressures

“…5, 28); however, vagal tone is normally low or even absent in reptiles anesthetized with barbiturates (e.g., Refs. 10,16). Furthermore, because the hypoxic responses persisted after muscarinic receptor blockade by atropine in caimans (Fig.…”

“…The rattlesnake and the tegu lizard have undivided ventricles and, consequently, equal pressures in systemic and pulmonary circulation (Ref. 16; N. Skovgaard and T. Wang, unpublished observations on tegus). Their lungs are unicameral with a central air-filled cavity that opens radially into the parenchyma (26,32).…”

“…In contrast to mammals, the role of humoral and local factors in cardiovascular control remains largely unknown in reptiles. Recent studies, nevertheless, indicate that the pulmonary circulation is much less responsive to humoral and local factors than the systemic circulation (8,9,11,16,35,40).Lung structure and heart morphology vary substantially among reptiles. Most snakes and many lizards have unicameral and simple lungs, whereas the multicameral lungs in turtles, varanid lizards, and crocodilians are more complex and compartmentalized (26,31,32,34).…”

“…In contrast to mammals, the role of humoral and local factors in cardiovascular control remains largely unknown in reptiles. Recent studies, nevertheless, indicate that the pulmonary circulation is much less responsive to humoral and local factors than the systemic circulation (8,9,11,16,35,40).…”

Vagal tone regulates cardiac shunts during activity and at low temperatures in the South American rattlesnake, Crotalus durissus

“…In reptiles, activity in the vagal innervation of the pulmonary artery can massively reduce G pul and increased vagal tone can mediate large net R-L shunts (Burggren 1987;Luckhardt and Carlson 1921;Milsom et al 1977;Taylor et al 2009). Adrenergic control of systemic conductance (G sys ) may alter blood flow relations (Hicks 1994;Galli et al 2007), and many humoral factors such as nitric oxide (Crossley et al 2000;Galli et al 2005a), bradykinin (Galli et al 2005b) and adenosine (Joyce and Wang 2014) have also been demonstrated to affect cardiac shunt patterns. Thus, as the relative importance of central regulation of cardiac shunt patterns through vagal innervation of the pulmonary artery remains uncertain, it is pertinent to re-evaluate whether the vagus accounts for significant changes in cardiac shunts to respond to alterations in metabolic demand in conscious organisms.…”