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Dissociation between the increase in systemic vascular resistance induced by acute nitric oxide synthesis inhibition
A Zappellini1, H Moreno Júnior, E Antunes
1Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, (SP), Brazil.
Abstract:
The decrease in cardiac output (CO) that follows nitric oxide (NO) synthesis inhibition is thought to be the result of an increase in systemic vascular resistance (SVR). We investigated whether sodium nitroprusside (SNP) and iloprost prevent the decrease in CO induced by short-term administration of N omega-nitro-L-arginine methyl ester (L-NAME) in anesthetized dogs. The left femoral artery and vein were cannulated for mean arterial blood pressure (MABP) measurement and drug administration, respectively. A Swan-Ganz thermodilution catheter was inserted into the right femoral vein and allowed the determination of CO and the calculation of SVR, expressed as the cardiac index (CI) and the index of systemic vascular resistance (ISVR), respectively. L-NAME (0.01-10.0 mg/kg; n = 13) induced dose-dependent increases in MABP and in the ISVR. These changes were accompanied by significant decreases in both the CI and the heart rate. SNP (1 microgram/kg/min; n = 6) virtually abolished L-NAME-induced hypertension and significantly attenuated both the increase in the ISVR (< 3.0 mg/kg) and the decrease in CO. Iloprost (50 ng/kg/min; n = 6) also abolished L-NAME-induced hypertension and markedly attenuated the increase in SVR. However, the decrease in CO was not prevented by this vasodilator. These results clearly demonstrate that the increase in SVR is not the major factor accounting for the decrease in CO after short-term NO synthesis inhibition in anesthetized dogs.
Insights
Nitric oxide (NO) synthesis inhibition decreases cardiac output (CO) by increasing systemic vascular resistance (SVR). Vasodilators sodium nitroprusside and iloprost reduced hypertension but did not prevent the CO decrease, indicating SVR is not the primary cause.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
Background:
- Nitric oxide (NO) plays a crucial role in regulating vascular tone.
- Inhibition of NO synthesis is known to increase systemic vascular resistance (SVR) and decrease cardiac output (CO).
Purpose of the Study:
- To investigate the role of systemic vascular resistance (SVR) in the decrease of cardiac output (CO) following nitric oxide (NO) synthesis inhibition.
- To determine if vasodilators sodium nitroprusside (SNP) and iloprost can prevent the reduction in CO induced by L-NAME.
Main Methods:
- Anesthetized dogs were administered N omega-nitro-L-arginine methyl ester (L-NAME) to inhibit NO synthesis.
- Cardiac output (CO), systemic vascular resistance (SVR), mean arterial blood pressure (MABP), and heart rate were measured.
- The effects of SNP and iloprost on these parameters were evaluated.
Main Results:
- L-NAME induced a dose-dependent increase in MABP and SVR, accompanied by a decrease in CO and heart rate.
- SNP and iloprost abolished L-NAME-induced hypertension and attenuated the increase in SVR.
- Neither SNP nor iloprost prevented the decrease in CO induced by L-NAME.
Conclusions:
- The increase in systemic vascular resistance (SVR) is not the primary factor responsible for the decrease in cardiac output (CO) after short-term NO synthesis inhibition.
- Vasodilators can mitigate hypertension and SVR increases but do not restore cardiac output in this model.