Differentiation of neurogenic and myocardial angiotensin II receptors in isolated rabbit atria.

Abstract

The effect of angiotensin on the action of tyramine was studied in isolated rabbit left atria paced by point and field stimulation to more clearly define the interaction of angiotensin with the sympathetic nervous system. Administration of angiotensin resulted in similar increases in contractility in both point- and field-stimulated atria. In point-stimulated preparations only the muscle is stimulated to contract, whereas in field-stimulated preparations both nerve and muscle are stimulated. 1-Sar-8-Ala-angiotensin II completely blocked the direct inotropic effect of angiotensin in a molar dose ratio of 3:1 in both point- and field-stimulated preparations. However, angiotensin (0.05-10 ng/ml) potentiated the inotropic effect of tyramine in field-stimulated atria only. This facilitatory effect was not inhibited by 1-Sar-8-Ala-angiotensin II at a molar dose ratio of 3:1; indeed, a ratio of 500:1 was necessary for complete blockade of this angiotensin-induced potentiation. This antagonist in odses of 0.1-1000 ng/ml was without contractile effect in any preparation, regardless of whether tyramine was present. The data suggest the presence of (1) a presynaptic angiotensin receptor that, in the presence of sympathetic nerve stimulation, modulates the release of norepinephrine and (2) a second angiotensin receptor in cardiac tissue that directly influences myocardial contractility.

Differential gene expression and regulation of angiotensin II receptor subtypes in rat cardiac fibroblasts and cardiomyocytes in culture.

“…Subnanomolar concentrations ofAngIl facilitates adrenergic neurotransmission in the heart ( 15), indirectly leading to an increase in the heart rate, contractility, and a decrease in coronary flow ( 15,16). The majority ofthe cardiovascular and hormone modulating actions ofAng1I in the adult animal are mediated through the ATI-R (2).…”

Inhibition of the vagal component of the baroreceptor‐cardioinhibitory reflex by angiotensin III in dogs and sheep.

“…Lewis & Reit, 1965;Farr & Grupp, 1967;Aiken & Reit, 1968;Hughes & Roth, 1971;Blumberg, Ackerly & Peach, 1975) and to inhibit the parasympathetic nervous system centrally (Scroop & Lowe, 1969;Lumbers, McCloskey & Potter, 1979) and peripherally (Potter, 1982).…”

Adrenergic Facilitation by Angiotensin: Does it Serve a Physiological Function?

“…Angiotensin antagonists interfere with peripheral adrenergic facilitation and thus it would appear that angiotensin receptors mediate peripheral adrenergic facilitation (Westfall, 1977). According to one study on rabbit heart the susceptibility to blockade of presynaptic angiotensin receptors was much less than that of the postsynaptic receptors (Blumberg, Ackerly & Peach, 1975). The antagonist/agonist ratio was 500: 1 for almost complete blockade of the presynaptic effect.…”