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The left ventricular contractility of the rat heart is modulated by changes in flow and alpha 1-adrenoceptor
P F Vassallo1, I Stefanon, L V Rossoni
1Departamento de Ciências Fisiológicas, Centro Biomédico, Universidade Federal do Espírito Santo, Vitória, Brasil. daltonv2@interlink.com.br
Insights
Sympathetic stimulation via norepinephrine enhances cardiac contractility through alpha 1-adrenoceptor activation and increased coronary perfusion pressure (CPP). Both direct receptor stimulation and elevated flow contribute synergistically to improved myocardial performance.
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Background:
- Myocardial contractility is influenced by coronary perfusion pressure (CPP) and alpha 1-adrenoceptor stimulation.
- Norepinephrine mediates sympathetic effects, increasing heart contractility and arterial pressure, thereby affecting CPP.
- Clarifying the individual and combined contributions of these factors to myocardial performance is crucial.
Purpose of the Study:
- To investigate the independent and combined effects of alpha 1-adrenergic stimulation and altered coronary flow on myocardial contractility.
- To elucidate the mechanisms underlying norepinephrine-induced increases in cardiac performance.
Main Methods:
- Protocol 1: In vivo assessment in anesthetized rats measuring arterial pressure and left ventricular pressure changes following phenylephrine (PE) stimulation, with and without beta- and muscarinic receptor blockade.
- Protocol 2: Ex vivo Langendorff perfused rat hearts measuring isovolumic systolic pressure (ISP) and CPP under varying flow rates, with and without PE and nitroprusside (NP) treatment.
Main Results:
- In vivo alpha 1-adrenergic stimulation with PE significantly increased left ventricular developed pressure and arterial blood pressure.
- In isolated hearts, both CPP and ISP increased with flow rate.
- Drug treatments did not alter CPP, but PE and PE + NP significantly increased ISP, with the greatest increase observed with PE + NP.
Conclusions:
- Alpha 1-adrenergic stimulation directly enhances myocardial contractility.
- Increased coronary perfusion pressure and flow also contribute to improved cardiac performance.
- These mechanisms act both independently and synergistically to augment myocardial function.
Abstract:
Myocardial contractility depends on several mechanisms such as coronary perfusion pressure (CPP) and flow as well as on alpha 1-adrenoceptor stimulation. Both effects occur during the sympathetic stimulation mediated by norepinephrine. Norepinephrine increases force development in the heart and produces vasoconstriction increasing arterial pressure and, in turn, CPP. The contribution of each of these factors to the increase in myocardial performance needs to be clarified. Thus, in the present study we used two protocols: in the first we measured mean arterial pressure, left ventricular pressure and rate of rise of left ventricular pressure development in anesthetized rats (N = 10) submitted to phenylephrine (PE) stimulation before and after propranolol plus atropine treatment. These observations showed that in vivo alpha 1-adrenergic stimulation increases left ventricular developed pressure (P < 0.05) together with arterial blood pressure (P < 0.05). In the second protocol, we measured left ventricular isovolumic systolic pressure (ISP) and CPP in Langendorff constant flow-perfused hearts. The hearts (N = 7) were perfused with increasing flow rates under control conditions and PE or PE + nitroprusside (NP). Both CPP and ISP increased (P < 0.01) as a function of flow. CPP changes were not affected by drug treatment but ISP increased (P < 0.01). The largest ISP increase was obtained with PE + NP treatment (P < 0.01). The results suggest that both mechanisms, i.e., direct stimulation of myocardial alpha 1-adrenoceptors and increased flow, increased cardiac performance acting simultaneously and synergistically.