Hypotensive action of captopril in spontaneously hypertensive and normotensive rats. Interference with neurogenic vasoconstriction.

Abstract

The effects of captopril and angiotensin II on adrenergic neurotransmission have been studied in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). In a pithed rat preparation, vasoconstrictor responses evoked by spinal stimulation were greater in SHR than WKY (p < 0.01). Captopril reduced responses to electrical stimulation and this reduction was greater in the SHR (p < 0.001). Bilateral nephrectomy reduced the vasoconstrictor responses to nerve stimulation in both strains of rat and abolished the effects of captopril. In an isolated perfused mesenteric artery preparation, responses to nerve stimulation in the absence of angiotensin II were greater in SHR than WKY (p < 0.05). Angiotensin II potentiated responses from both strains of rat, however the amplitude of the potentiation was greater in preparations from the SHR than those from WKY (p < 0.002). Captopril (30 mg/kg by mouth) reduced blood pressure in conscious SHR over a 5-day dosing period. In WKY rats, no hypotensive action of captopril was observed. However, in another normotensive strain, the Alderley Park Wistar rat (APW), captopril lowered blood pressure. Plasma renin activity was not significantly different among these three strains of rat. The APW have previously been shown to be very sensitive to the adrenergic potentiating actions of angiotensin II. Captopril thus lowers blood pressure in SHR and APW, and both these strains are sensitive to the adrenergic potentiating actions of angiotensin II. It does not lower blood pressure in WKY, which is relatively insensitive to these actions of the octapeptide. Therefore, the hypotensive action of captopril in the rat may be due to its interference with the adrenergic potentiating effect of angiotensin II. (Hypertension 4: 764-772, 1982) KEY WORDS • angiotensin • converting enzyme inhibition • pithed rat perfused rat mesenteric artery • sympathetic nervous system * adrenergic vasoconstriction • plasma renin activity • blood pressure • captopril T HE mechanism of action of captopril in lowering blood pressure is unclear. In both humans and animals, a fall in blood pressure is seen in those with elevated, normal, and low levels of circulating renin. 1 "* This could suggest that the inhibition of angiotensin II formation is not an important factor in the hypotensive action of captopril. However, recent studies suggest that the level of angiotensin II that participates in the control of blood pressure is closer to the normal range than previously realized. 7 ' 8 In addition , a functional interaction of the octapeptide with the sympathetic nervous system has been largely over

Central injection of captopril inhibits the blood pressure response to intracerebroventricular choline

“…Intracerebroventricular injections of renin-angiotensin system antagonists decrease blood pressure in spontaneously hypertensive and normotensive rats (9,17,19,20,32,33). We also confirmed that captopril, an angiotensin-converting enzyme inhibitor, decreases blood pressure in a dose-dependent manner.…”

Effect of lisinopril on tissue levels of neuropeptide Y in normotensive and spontaneously hypertensive rats

“…Pressor responses to NA in SHR are similar to those of control rats, but neurogenic vasoconstrictor responses are greater in SHR. 12 Interestingly, ACE inhibition produces a greater attenuation of nerve stimulated responses in SHR compared to control. 12 Acutely, inhibition of AII formation may alter the release of sympathetic neurotransmitters or may have a direct action on effector cell-responsiveness.…”

“…12 Interestingly, ACE inhibition produces a greater attenuation of nerve stimulated responses in SHR compared to control. 12 Acutely, inhibition of AII formation may alter the release of sympathetic neurotransmitters or may have a direct action on effector cell-responsiveness. [3][4][5][6] With chronic ACE inhibition transmitter synthesis may be altered or other actions resulting in structural changes in the vasculature may occur.…”

Captopril reduces aortic and microvascular growth in hypertensive and normotensive rats.

“…32 Increased Ang II levels within the vascular wall could influence vascular growth, either by direct effects on vascular smooth muscle as discussed above or indirectly by potentiation of sympathetic activity. 33 - 34 Norepinephrine and epinephrine have been shown to increase the growth rate of cultured vascular SMCs, 35 and the sympathetic nervous system has a role in vascular SMC growth in hypertension. 36 The blockade of Ang II formation by captopril in SHR has an effect on the vascular wall over and above that predicted by its blood pressure-lowering effect.…”