Hypoxia and angiotensin II infusion redistribute lung blood flow in lambs

To assess the effects of alveolar hypoxia and angiotensin II infusion on distribution of blood flow to the lung we performed perfusion lung scans on anesthetized mechanically ventilated lambs. Scans were obtained by injecting 1-2 mCi of technetium-labeled albumin macroaggregates as the lambs were ventilated with air, with 10-14% O2 in N2, or with air while receiving angiotensin II intravenously. We found that both alveolar hypoxia and infusion of angiotensin II increased pulmonary vascular resistance and redistributed blood flow from the mid and lower lung regions towards the upper posterior region of the lung. We assessed the effects of angiotensin II infusion on filtration pressure in six lambs by measuring the rate of lung lymph flow and the protein concentration of samples of lung lymph. We found that angiotensin II infusion increased pulmonary arterial pressure 50%, lung lymph flow 90%, and decreased the concentration of protein in lymph relative to plasma. These results are identical to those seen when filtration pressure increases during alveolar hypoxia. We conclude that alveolar hypoxia and angiotensin II infusion both increase fluid filtration in the lung by increasing filtration pressure. The increase in filtration pressure may be the result of a redistribution of blood flow in the lung with relative overperfusion of vessels in some areas and transmission of the elevated pulmonary arterial pressure to fluid-exchanging sites in those vessels.     

Methylene blue selectively inhibits pulmonary vasodilator responses in cats

The effects of methylene blue on vascular tone and the responses to pressor and depressor substances were investigated in the constricted feline pulmonary vascular bed under conditions of controlled blood flow and constant left atrial pressure. When tone was elevated with U46619, intralobar injections of acetylcholine, bradykinin, nitroglycerin, isoproterenol, epinephrine, and 8-bromoguanosine-3',5'-cyclic monophosphate (8-bromo-cGMP) dilated the pulmonary vascular bed. Intralobar infusions of methylene blue elevated lobar arterial pressure without altering base-line left atrial or aortic pressure, heart rate, or cardiac output. When methylene blue was infused in concentrations that raised lobar arterial pressure to values similar to those attained during U46619 infusion, the pulmonary vasodilator responses to acetylcholine, bradykinin, and nitroglycerin were reduced significantly, whereas vasodilator responses to isoproterenol, epinephrine, and 8-bromo-cGMP were not altered. Moreover, the pressor responses to angiotensin II and BAY K 8644 during U46619 infusion and during methylene blue infusion were similar. The enhancing effects of methylene blue on vascular tone and inhibiting effects of this agent on responses to acetylcholine, bradykinin, and nitroglycerin were reversible. These responses returned to control value when tone was again increased with U46619, 30-45 min after the methylene blue infusion was terminated. The present data are consistent with the hypothesis that cGMP may play a role in the regulation of tone in the feline pulmonary vascular bed and in the mediation of vasodilator responses to the endothelium-dependent vasodilators, acetylcholine and bradykinin, and to nitrogen oxide-containing vasodilators such as nitroglycerin.     

Comparison of two methods of altering blood pressures for assessing neonatal cerebral blood flow autoregulation

The cerebral blood flow of newborn lambs at reduced and elevated arterial blood pressures, induced by intravenous infusion of sodium nitroprusside and phenylephrine hydrochloride as well as blood withdrawal and reinfusion, were compared. Both blood withdrawal and sodium nitroprusside infusion reduced mean arterial pressure from 83 to 60 mmHg (1 mmHg = 133 Pa). Reinfusion of blood increased arterial pressure to 94 mmHg. Phenylephrine hydrochloride infusion increased arterial pressure to 102 mmHg. The cerebral blood flows at corresponding arterial pressures were similar (coefficient of correlation = 0.88, P less than 0.01). Cerebral blood flow before and after infusion of phenylephrine hydrochloride and sodium nitroprusside into the brain via the carotid artery did not change. The results indicate that blood-borne phenylephrine hydrochloride and sodium nitroprusside, in concentrations that would alter arterial blood pressure significantly from its resting level, do not change cerebral blood flow directly.     

Release of atriopeptin in the rat by vasoconstrictors or water immersion correlates with changes in right atrial pressure

Vasopressin, its 1-deamino analog (dAVP), angiotensin II, and phenylephrine, administered intravenously, increased plasma atriopeptin immunoreactivity in chloral hydrate-anesthetized rats. A continuous one hour infusion of either dAVP or phenylephrine caused a sustained elevation in: a) systemic blood pressure; b) right atrial pressure; c) left ventricular end diastolic pressure; and d) plasma atriopeptin immunoreactivity. While continuous infusion of angiotensin II also produced a sustained elevation in left ventricular end diastolic pressure, the changes in right atrial pressure and plasma atriopeptin were only transient. These data suggest that plasma atriopeptin most closely correlates with right atrial pressure. Consistent with this hypothesis, we found that the release of atriopeptin directly correlated with changes in right atrial pressure in anesthetized, water-immersed rats.     

Effect of angiotensin II and peptide YY on cerebral and circumventricular blood flow

Angiotensin II and peptide YY (PYY) are putative neuro/humoral agents acting at several circumventricular regions. These peptides also constrict cerebral vessels. We examined the effect of acute intravenous infusion of saline, angiotensin II and peptide YY on local cerebral blood flow (14C-iodoantipyrine autoradiography) in the circumventricular and non-circumventricular brain regions of 17 conscious rats. No reductions in brain blood flow (28 regions) were observed although angiotensin II and PYY infusion elevated arterial blood pressure 15-25% without influencing heart rate, suggesting an increase in peripheral resistance. However, local blood flow was dependent on the peptide infused. During PYY infusion, blood flow was rather constant in the 20 non-circumventricular regions examined whereas an increase in blood flow and a slight decrease in cerebrovascular resistance occurred in the circumventricular regions. The area postrema exhibited the most pronounced changes--an elevation in blood flow of 44 +/- 11% and a reduction in resistance of 20 +/- 5% in comparison to that in control animals. During angiotensin II infusion, local cerebral blood flow was similar to that in controls and local cerebrovascular resistance was elevated. Thus, the local cerebral circulatory response to peptide administration was dependent on the location of the region examined (circumventricular or non-circumventricular) and on the vasoactive peptide infused.     

Adaptation of active tone in the mouse descending thoracic aorta under acute changes in loading

Arteries can adapt to sustained changes in blood pressure and flow, and it is thought that these adaptive processes often begin with an altered smooth muscle cell activity that precedes any detectable changes in the passive wall components. Yet, due to the intrinsic coupling between the active and passive properties of the arterial wall, it has been difficult to delineate the adaptive contributions of active smooth muscle. To address this need, we used a novel experimental–computational approach to quantify adaptive functions of active smooth muscle in arterial rings excised from the proximal descending thoracic aorta of mice and subjected to short-term sustained circumferential stretches while stimulated with various agonists. A new mathematical model of the adaptive processes was derived and fit to data to describe and predict the effects of active tone adaptation. It was found that active tone was maintained when the artery was adapted close to the optimal stretch for maximal active force production, but it was reduced when adapted below the optimal stretch; there was no significant change in passive behavior in either case. Such active adaptations occurred only upon smooth muscle stimulation with phenylephrine, however, not stimulation with KCl or angiotensin II. Numerical simulations using the proposed model suggested further that active tone adaptation in vascular smooth muscle could play a stabilizing role for wall stress in large elastic arteries.     

Effect of dopamine on gastric smooth muscle in rats and characteristics of the alpha-adrenoreceptors of gastrointestinal tract muscle cells

Dopamine and phenylephrine decreased the tone of the smooth muscles of the isolated rat stomach strips in concentractions of 10(-6) M and higher. The curves of the concentration-effect have the same slope. Dopamine effects are unchanged in the presence of propranolole (5.10(-6) g/ml). Phentholamine (as well as dihydroergotamine and tropaphen) shows an equal degree of antagonism towards both phenylephrine and dopamine. It is suggested that dopamine and phenylephrine relax the stomach muscles by influencing the alpha-adrenoreceptors. The latter differe from alpha-adrenoreceptors of the ejaculatory duct of rats by a high sensitivity to the blocking influence of some neuroleptics--haloperidol, trifluoperazine, chlorpromazine, pA2 for which (8.11--8.64) is of the same range as pA2 for alpha-adrenolytic drugs (7.76--8.46). The features of resemblance and difference between alpha-adrenoreceptors of the gastrointestinal tract muscles and the inhibitory dopamine receptors of the nerve cells are being discussed.     

Capillary filtration coefficient is independent of number of perfused capillaries in cat skeletal muscle

The capillary filtration coefficient (CFC) is assumed to reflect both microvascular hydraulic conductivity and the number of perfused capillaries at a given moment (precapillary sphincter activity). Estimation of hydraulic conductivity in vivo with the CFC method has therefore been performed under conditions of unchanged vascular tone and metabolic influence. There are studies, however, that did not show any change in CFC after changes in vascular tone and metabolic influence, and these studies indicate that CFC may not be influenced by alteration in the number of perfused capillaries. The present study reexamined to what extent CFC in a pressure-controlled preparation depends on the vascular tone and number of perfused capillaries by analyzing how CFC is influenced by 1) vasoconstriction, 2) increase in metabolic influence by decrease in arterial blood pressure, and 3) occlusion of precapillary microvessels by arterial infusion of microspheres. CFC was calculated from the filtration rate induced by a fixed decrease in tissue pressure. Vascular tone was increased in two steps by norepinephrine (n = 7) or angiotensin II (n = 6), causing a blood flow reduction from 7.2 +/- 0.8 to at most 2.7 +/- 0.2 ml x min(-1) x 100 g(-1) (P < 0.05). The decrease in arterial pressure reduced blood flow from 4.8 +/- 0.4 to 1.40 +/- 0.1 ml x min(-1) x 100 g(-1) (n = 6). Vascular resistance increased to 990 +/- 260% of control after the infusion of microspheres (n = 6). CFC was not significantly altered from control after any of the experimental interventions. We conclude that CFC under these conditions is independent of the vascular tone and number of perfused capillaries and that variation in CFC reflects variation in microvascular hydraulic conductivity.     

The effect of prostaglandin E2 on the cardiovascular response to angiotensin II in pregnant rabbits

The rise in arterial blood pressure in response to angiotensin II was studied in the last third of pregnancy in rabbits. The response was compared with that of pregnant rabbits during infusion of prostaglandin E₂ and F_2α. Prostaglandin E₂ significantly diminished the rise in diastolic pressure in response to angiotensin II. Prostaglandin F_2α did not alter the response. Intravenous indomethacin elevated the blood pressure and caused an absolute increase in the pressor response. It did not mediate a change in the percentage rise in blood pressure in response to angiotensin II.     

Acute hypertension inhibits thirst stimulated by ANG II, hyperosmolality, or hypovolemia in rats

The present study sought to determine whether increases in arterial blood pressure inhibited drinking behavior evoked by ANG II, hyperosmolality, or hypovolemia in rats. Cumulative water intakes in 60- or 90-min tests and latency to the first lick were recorded as indexes of thirst. During intravenous infusions of 100 ng. kg(-1). min(-1) ANG II, attenuation of the induced increases in arterial pressure with the arteriolar vasodilator diazoxide resulted in greater water intakes and shorter latencies to drink. Drinking behavior stimulated by intravenous infusion of hypertonic saline was significantly inhibited by increases in arterial pressure caused by intravenous infusion of phenylephrine or endothelin-1, and this inhibition of drinking was proportional to the induced increase in pressure. Upon termination of the phenylephrine infusion, mean arterial pressure returned to basal values, and drinking was restored. Phenylephrine-induced increases in arterial pressure also inhibited drinking behavior in response to hypovolemia that could not be explained by differences in plasma renin activity, plasma protein concentration, or plasma osmolality. Thus increases in arterial pressure inhibit water drinking behavior in response to each of these three thirst stimuli in rats.     

Hypotensive effect of angiotensin II after AT1-receptor blockade with losartan.

Recent data suggest that hypotensive effect of losartan may not be attributed solely to AT1-receptor blockade, but also to excessive AT2 or other receptors stimulation by elevated angiotensin II and its derivative peptides. Therefore in the present study we examined the effect of angiotensin II on mean blood pressure after AT -receptor blockade with losartan. Male Wistar rats were anaesthetised and received injection of either losartan (30 mg/kg, 1 ml/kg, i.v.) or saline (the same volume and route) followed by bolus injection of angiotensin II (100, 300 or 1,000 ng/kg; 1 ml/kg, i.v.) or 1-hour infusion of angiotensin II (200 ng/kg/min; 2.5 ml/kg/h, i.v.). Control animals received saline instead. Angiotensin II, given either as the injection or the infusion, caused an evident increase in mean blood pressure (p ranged from 0.05 to 0.001 depending on the experimental group). Losartan caused a rapid drop in mean blood pressure and blunted the hypertensive effect of angiotensin II (p < 0.01). Moreover, in the losartan-pretreated animals the hypotensive phase was enhanced by the infusion, but not single injection of angiotensin II, which was most evident from the 30 th minute of observation (p < 0.05 vs control). In conclusion, hypotensive effect of losartan may be amplified by simultaneous increase in angiotensin II level, the situation observed during chronic AT1-receptor blockade.     

The actions of vasoactive compounds in the foetus and the effect of perfusion through the placenta on their biological activity

In acute experiments on the in utero foetal lamb, angiotensin II was a more potent pressor agent that either noradrenaline or adrenaline, and the response to angiotensin II was not consistently modified by the combined administration of alpha and beta-adrenergic blocking agents. A significant reduction in the pressor response of the foetus to angiotensin II and noradrenaline occurred with infusion of these compounds to the foetus by the umbilical artery when compared with the response obtained with infusions of the same doses of these drugs by the umbilical vein. Moreover, the concentration of angiotensin II (pg. ml-1) present in the foetal circulation was less following umbilical arterial infusions compared with umbilical vein infusions of the same doses. A similar reduction in the pressor activity of adrenaline and the cardio-stimulant effect of isoprenaline occurred when these drugs were infused by the umbilical artery. It is concluded that the foetus, like the adult animal, is more sensitive to angiotensin II than to catecholamines and that the biological activities of noradrenaline, angiotensin II, adrenaline and isoprenaline are reduced by perfusion through the foetal placenta.     

Analysis of pulmonary vasodilator responses to the Rho-kinase inhibitor fasudil in the anesthetized rat

The small GTP-binding protein Rho and its downstream effector, Rho-kinase, are important regulators of vasoconstrictor tone. Rho-kinase is upregulated in experimental models of pulmonary hypertension, and Rho-kinase inhibitors decrease pulmonary arterial pressure in rodents with monocrotaline and chronic hypoxia-induced pulmonary hypertension. However, less is known about responses to fasudil when pulmonary vascular resistance is elevated on an acute basis by vasoconstrictor agents and ventilatory hypoxia. In the present study, intravenous injections of fasudil reversed pulmonary hypertensive responses to intravenous infusion of the thromboxane receptor agonist, U-46619 and ventilation with a 10% O(2) gas mixture and inhibited pulmonary vasoconstrictor responses to intravenous injections of angiotensin II, BAY K 8644, and U-46619 without prior exposure to agonists, which can upregulate Rho-kinase activity. The calcium channel blocker isradipine and fasudil had similar effects and in small doses had additive effects in blunting vasoconstrictor responses, suggesting parallel and series mechanisms in the lung. When pulmonary vascular resistance was increased with U-46619, fasudil produced similar decreases in pulmonary and systemic arterial pressure, whereas isradipine produced greater decreases in systemic arterial pressure. The hypoxic pressor response was enhanced by 5-10 mg/kg iv nitro-L-arginine methyl ester (L-NAME), and fasudil or isradipine reversed the pulmonary hypertensive response to hypoxia in control and in L-NAME-treated animals, suggesting that the response is mediated by Rho-kinase and L-type Ca(2+) channels. These results suggest that Rho-kinase is constitutively active in regulating baseline tone and vasoconstrictor responses in the lung under physiological conditions and that Rho-kinase inhibition attenuates pulmonary vasoconstrictor responses to agents that act by different mechanisms without prior exposure to the agonist.     

Acute effects of ethanol on baroreceptor reflex control of heart rate and on pressor and depressor responsiveness in rats

In rats anesthetized with alpha-chloralose, doses of 0.1, 0.5, and 1 g/kg of ethanol produced an upward shift of baroreflex curves constructed by plotting the heart rate response against mean arterial pressure following evoked rises in mean arterial pressures by phenylephrine or angiotensin II. Whereas the upward shift of baroreceptor curves may be related, at least in part, to a higher base-line heart rate after ethanol, the data showed that the 1 g/kg dose of ethanol significantly depressed baroreflex sensitivity, suggesting that higher doses of ethanol impair baroreflex-mediated bradycardia. The phenylephrine, but not the angiotensin II or the nitroprusside, dose-response curves were shifted to the right after ethanol, indicating a decreased pressor responsiveness and suggesting that ethanol may have alpha-adrenergic blocking activity. This effect was also obtained in conscious rats. That this effect was not influenced by changes in baroreflex sensitivity was supported by the finding that a similar shift of the phenylephrine pressor-response curve was obtained in bilaterally vagotomized and hexamethonium-treated rats. Whether this effect of ethanol on baroreflex control of heart rate was influenced by anesthesia was investigated in conscious rats; the 1 g/kg dose of ethanol that produced the most significant decrease in baroreflex sensitivity was used in these experiments. Ethanol was still able to significantly inhibit baroreflex sensitivity in conscious rats, but the upward shift of the baroreflex curve and the elevated base-line heart rate no longer occurred.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of baroreflex in the pressor response of rats with hypertension developed by renal artery stenosis

We examined the interrelationships between the pressor response to the administration of norepinephrine and arginine vasopressin and baroreflex function in rats with hypertension of two days' duration induced by heminephrectomy and a clip placed on the right renal artery (2-day clipped rats). Mean arterial pressure was higher in the 2-day clipped rats than in heminephrectomized rats without clips (sham-operated rats). The pressor response in the 2-day clipped rats to both agents increased as compared to the sham-operated rats. This hyperresponsiveness was attenuated by administering an angiotensin II antagonist, [1-Sar, 8-Ile] angiotensin II. Baroreflex sensitivity was studied by measuring changes in arterial pressure and pulse interval in response to the injection of phenylephrine. Baroreflex sensitivity was not decreased but markedly increased in the 2-day clipped rats and unaffected by infusing the angiotensin II antagonist. These results provide evidence that 1) in the 2-day clipped rats there are exaggerated pressor responses to vasoconstrictors; 2) the hyperresponsiveness is not causally related to the change of baroreflex sensitivity; and 3) angiotensin II plays a significant role in the increased pressor responses; however, the baroreflex mechanism is not involved in attenuation of the hyperresponsiveness by the angiotensin II antagonist.     

N omega-nitro-L-arginine methyl ester selectively inhibits pulmonary vasodilator responses to acetylcholine and bradykinin.

The effects of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of endothelium-derived relaxing factor (EDRF) production, on vascular tone and responses were investigated in the pulmonary vascular bed of the intact-chest cat under conditions of controlled blood flow and constant left atrial pressure. When pulmonary vascular tone was elevated with U-46619, intralobar injections of acetylcholine, bradykinin, sodium nitroprusside, isoproterenol, prostaglandin E1 (PGE1), lemakalim, and 8-bromo-guanosine 3',5'-cyclic monophosphate (8-bromo-cGMP) dilated the pulmonary vascular bed. Intravenous administration of L-NAME elevated lobar arterial and systemic arterial pressures without altering left atrial pressure. When U-46619 was infused after L-NAME to raise lobar arterial pressure to levels similar to those attained during the control period, vasodilator responses to acetylcholine and bradykinin were reduced significantly, whereas responses to PGE1, lemakalim, and 8-bromo-cGMP were not altered, and responses to nitroprusside were increased. There was a small effect on the response to the highest dose of isoproterenol, and pressor responses to BAY K 8644 and angiotensin II were not altered. These results are consistent with the hypothesis that EDRF production may involve the formation of nitric oxide or a nitroso compound from L-arginine and that EDRF production may have a role in the regulation of tone and in the mediation of responses to acetylcholine and bradykinin in the pulmonary vascular bed of the cat.     

Blockade of the pre- and postjunctional effects of angiotensin in vivo with a non-peptide angiotensin receptor antagonist

Recent reports indicate that some imidazole-5-acetic acid derivatives are competitive antagonists of angiotensin II receptors. However, to our knowledge, there is no published information regarding: 1) what constant infusion rate of these non-peptide angiotensin receptor blockers is necessary to effectively antagonize angiotensin receptors in vivo, 2) whether imidazole-5-acetic acid derivatives antagonize both prejunctional and postjunctional angiotensin receptors, and 3) whether effective levels of these compounds exert non-specific actions and/or partial agonist activity. To address these issues, either vehicle, 2-butyl-4-chloro-1-(2-nitrobenzyl) imidazole-5-acetic acid (CV-2961; 30 and 100 micrograms/min) or a standard angiotensin receptor blocker, 1Sar8Ile-angiotensin II (100 ng/min), was infused intravenously into captopril-treated rats that were prepared for in situ perfusion of their mesenteric vascular beds. Infusion of CV-2961 for two and one-half hours did not alter arterial blood pressure, mesenteric perfusion pressure, plasma aldosterone level, or mesenteric vascular responses to sympathetic nerve stimulation or exogenous norepinephrine. The higher dose of CV-2961 (100 micrograms/min) completely blocked angiotensin II-induced enhancement of vascular responses to sympathetic nerve stimulation and shifted the angiotensin dose-response curve 10-fold to the right with respect to angiotensin II-induced increases in mesenteric perfusion pressure. The effects of the lower dose of CV-2961 (30 micrograms/min) on these actions of angiotensin II were not statistically significant. 1Sar8Ile-angiotensin II abolished both the prejunctional and postjunctional effects of angiotensin II. We conclude that in intact rats CV-2961, infused at 100 micrograms/min, antagonizes both prejunctional and postjunctional angiotensin II receptors, yet has a somewhat greater effect on the prejunctional actions of angiotensin II. CV-2961 is devoid of partial agonist activity, and no non-specific actions of CV-2961 are evident. Imidazole-5-acetic acid derivatives may find considerable utility as pharmacological probes and as therapeutic agents.     

Effect of adrenoblockaders on vascular reactions in sinocarotid baroreflexes]

Blood pressure in the common carotid artery, the tone of the cerebral and femoral vessels were recorded by resistography in acute experiments on nonanesthetized cats (local anesthetics, listenon) with artificial respiration. The increased pressure in isolated carotid sinuses was accompanied by a decrease in arterial pressure and in the tone of the cerebral and femoral vessels. In both cases the reaction of the cerebral vessels was less pronounced as compared to that shown by the femoral vessels. The blocking of alpha-adrenoreceptors with phentolamine reduced or abolished completely the reactions noted. After beta-adrenergic blockade with obsidan these reactions persisted. The role of carotid baroceptors in the regulation of cerebral circulation under orthostatic collapse is discussed.     

Angiotensin II attenuates functional hyperemia in the mouse somatosensory cortex

We investigated whether angiotensin II (ANG II), a peptide that plays a central role in the genesis of hypertension, alters the coupling between synaptic activity and cerebral blood flow (CBF), a critical homeostatic mechanism that assures adequate cerebral perfusion to active brain regions. The somatosensory cortex was activated by stroking the facial whiskers in anesthetized C57BL/6J mice while local CBF was recorded by laser-Doppler flowmetry. Intravenous ANG II infusion (0.25 mug.kg-1.min-1) increased mean arterial pressure (MAP) from 82 +/- 2 to 102 +/- 3 mmHg (P < 0.05) without affecting resting CBF (P > 0.05). ANG II attenuated the CBF increase produced by whisker stimulation by 65% (P < 0.05) but did not affect the response to hypercapnia or to neocortical application of the nitric oxide donor S-nitroso-N-acetyl penicillamine (P > 0.05). The effect of ANG II on functional hyperemia persisted if the elevation in MAP was offset by controlled hemorrhage or prevented by topical application of the peptide to the activated cortex. ANG II did not reduce the amplitude of the P1 wave of the field potentials evoked by whisker stimulation (P > 0.05). Infusion of phenylephrine increased MAP (P > 0.05 from ANG II) but did not alter the functional hyperemic response (P > 0.05). The data suggest that ANG II alters the coupling between CBF and neural activity. The mechanisms of the effect are not related to the elevation in MAP and/or to inhibition of the synaptic activity evoked by whisker stimulation. The imbalance between CBF and neural activity induced by ANG II may alter the homeostasis of the neuronal microenvironment and contribute to brain dysfunction during ANG II-induced hypertension.     

Role of angiotensin II in oral contraceptive hypertension in anesthetized rats

Rats fed a diet containing an oral contraceptive estrogen-progestogen mixture (Enovid) for 26 weeks developed a significant (P<0.01) elevation in mean arterial pressure (145 ± 6 mm Hg) when compared to a control group of rats fed the same diet without oral contraceptive steroids (mean arterial pressure averaged 117 ± 6 mm Hg). Infusion of [Sar¹, Ala⁸] angiotensin II, a competitive antagonist of angiotensin II, reduced the mean arterial pressure (P<0.01) in the oral contraceptive-treated rats to 117 ± 9 mm Hg, while infusion of this angiotensin II analogue into the control rats did not lower the arterial pressure. These studies provided evidence that angiotensin II may be involved in the hypertension produced by Enovid treatment in rats.