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Neural effects on renal blood flow during acute hypotension vary with antihypertensive drugs
S Takishita1, H Muratani, N Kawazoe
1Third Department of Internal Medicine, University of the Ryukyus School of Medicine, Okinawa, Japan.
Abstract:
To examine the neural effects of antihypertensive drugs on renal blood flow, we measured blood flow and renal sympathetic nerve activity simultaneously in conscious spontaneously hypertensive rats aged 13 to 15 weeks. One to two days after surgery, intravenous administration of manidipine (calcium antagonist, n = 10), doxazosin (alpha 1-adrenergic receptor antagonist, n = 9), and clonidine (n = 7) lowered mean arterial pressure by at least 20% from baseline levels. Manidipine initiated a reduction of renal blood flow when mean pressure decreased by 20 +/- 2 mm Hg. At the maximal decrease in renal blood flow (mean pressure, -33 +/- 2 mm Hg), percent decrease in flow (-27 +/- 2%) significantly correlated with percent increase in renal nerve activity (+205 +/- 40%, r = -.878). Doxazosin began to decrease renal blood flow at a level of arterial pressure similar to that in manidipine treatment, whereas the maximal decrease in flow (-19 +/- 2%; mean pressure, -33 +/- 2 mm Hg; nerve activity, +225 +/- 44%) was significantly less than that in manidipine treatment. Although clonidine decreased arterial pressure and renal nerve activity, renal blood flow did not decrease even at the maximal decrease in mean pressure of 29 +/- 1 mm Hg. The addition of clonidine to manidipine treatment suppressed reflexly enhanced renal nerve activity and restored blood flow to the pretreatment level despite pronounced hypotension. These results clearly demonstrate that antihypertensive drugs with blocking action on renal nerve activity are capable of maintaining renal blood flow and that those associated with reflex-induced enhancement of nerve activity exert deteriorating effects on renal blood flow. Furthermore, a decrease in renal blood flow induced by calcium antagonists is mainly attributed to reflexly enhanced renal nerve activity.
Insights
Antihypertensive drugs affecting renal nerve activity impact renal blood flow differently. Drugs blocking nerve activity maintain flow, while those increasing it worsen renal blood flow, especially calcium antagonists.
Area of Science:
- Nephrology
- Pharmacology
- Cardiovascular Physiology
Background:
- Antihypertensive medications are crucial for managing hypertension.
- The neural regulation of renal blood flow is complex and can be influenced by drug actions.
- Understanding how different antihypertensive drug classes affect renal hemodynamics and nerve activity is vital for patient care.
Purpose of the Study:
- To investigate the impact of specific antihypertensive drugs on renal blood flow and renal sympathetic nerve activity.
- To differentiate the effects of calcium antagonists, alpha-1 adrenergic receptor antagonists, and centrally acting agents on renal hemodynamics.
- To elucidate the role of neural mechanisms in mediating drug-induced changes in renal blood flow.
Main Methods:
- Simultaneous measurement of renal blood flow and renal sympathetic nerve activity in conscious, spontaneously hypertensive rats.
- Intravenous administration of manidipine (calcium antagonist), doxazosin (alpha-1 adrenergic receptor antagonist), and clonidine.
- Assessment of drug effects on mean arterial pressure and renal nerve activity at various pressure reduction levels.
Main Results:
- Manidipine and doxazosin reduced renal blood flow, with a significant correlation between decreased flow and increased renal nerve activity for manidipine.
- Clonidine lowered blood pressure and nerve activity without decreasing renal blood flow.
- Combined clonidine and manidipine treatment maintained renal blood flow despite hypotension, indicating the protective role of nerve activity blockade.
Conclusions:
- Antihypertensive drugs that block renal nerve activity preserve renal blood flow.
- Drugs causing reflex enhancement of renal nerve activity negatively impact renal blood flow.
- Reduced renal blood flow associated with calcium antagonists is primarily due to reflexively increased renal nerve activity.