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Calcium antagonists: systemic and regional haemodynamic effects in conscious spontaneously hypertensive rats (SHR)
Insights
Calcium antagonists like verapamil and nifedipine lower blood pressure by dilating blood vessels, primarily in muscles. Baroreflex denervation reveals a broader vasodilatory effect across all vascular beds.
Area of Science:
- Cardiovascular Pharmacology
- Hypertension Research
- Pharmacodynamics
Background:
- Calcium antagonists are widely used antihypertensive agents.
- Their precise regional haemodynamic effects, especially in hypertension, require further elucidation.
- Spontaneously hypertensive rats (SHR) serve as a relevant model for studying human hypertension.
Purpose of the Study:
- To investigate the systemic and regional haemodynamic effects of three calcium antagonists (verapamil, nifedipine, PY 108-068) in conscious SHR.
- To determine the influence of the baroreflex system on the vasodilatory actions of these agents.
- To compare the vascular effects across different regional beds (renal, mesenteric, hindquarter).
Main Methods:
- Utilized conscious, chronically instrumented spontaneously hypertensive rats (SHR).
- Administered verapamil, nifedipine, and PY 108-068 in a dose-dependent manner.
- Measured systemic and regional haemodynamics, including mean arterial pressure (MAP) and total peripheral resistance.
- Performed sinoaortic baroreflex denervation to assess baroreflex influence.
Main Results:
- All tested calcium antagonists induced a dose-dependent decrease in MAP and total peripheral resistance.
- In intact SHR, vasodilation was predominantly observed in the hindquarter (muscular) vascular bed.
- Nifedipine and PY 108-068 elicited a reflex increase in cardiac output and heart rate, unlike verapamil.
- Following baroreflex denervation, the dose-response for blood pressure and resistance reduction shifted leftward.
- Baroreflex denervation revealed comparable vasodilation across renal, mesenteric, and hindquarter beds.
Conclusions:
- Calcium antagonists exhibit preferential vasodilation in the muscular vascular bed in intact spontaneously hypertensive rats.
- The baroreflex system modulates the regional distribution of vasodilatory effects induced by calcium antagonists.
- Sinoaortic baroreflex denervation unmasks a non-selective vasodilatory pattern, indicating the importance of reflex mechanisms in regional vascular responses.
Abstract:
The systemic and regional (renal, mesenteric and hindquarter) haemodynamic effects of the calcium antagonists verapamil, nifedipine and PY 108-068 [diethyl 4-(2, 1, 3-benzoxadiazol-4-yl)-1, 4-dihydro-2, 6-dimethylpyridine-3, 5-dicarboxylate] were studied in conscious, chronically instrumented spontaneously hypertensive rats (SHR). All three calcium antagonists caused a dose-dependent fall in mean arterial pressure (MAP) and total peripheral resistance. In intact animals the fall in resistance was related primarily to a vasodilatation in the hindquarter (mainly muscular) vascular bed. During the early fall in blood pressure a reflex rise in cardiac output and heart rate was observed following nifedipine and PY 108-068, but not after verapamil. Following sinoaortic baroreflex denervation the dose-response curve for the calcium antagonist-induced fall in blood pressure and total peripheral resistance was shifted to the left. Moreover, the calcium antagonists then caused a comparable degree of vasodilation in all three vascular beds studied. It is concluded that calcium antagonists preferentially dilate the muscular bed in intact animals; however, sinoaortic baroreflex denervation unmasks an unselective pattern of vasodilatation.