Angiotensin in the rat has twofold action: a constrictor effect on the arterioles, and a stimulating effect on the heart. Peptide chemists already engaged with modifications of natural molecules became interested in clarifying the following problems: Which chemically functional or nonfunctional groups are essential for biological activity, or what special structural requirements are responsible for an attachment to a hypothetical receptor? The E-mail message field is required. It deals with hypotensive peptides and with eiizynies which liberate them. Several specific kinin receptor antagonists are being developed with the major interest in treating these pathological conditions to block the activation of kinin receptors. These bone lesions may be a source of considerable clinical concern unless their true benign nature is recognized.
In another series of experiments the dynamics of vasomotor activity were studied after the same treatment by the split-image method. The response of the vascular bed was directly proportional to the perfusion pressure, but at a given pressure no difference was seen between blocked and unblocked animals. In the blocked animal the vasodilator effect of bradykinin is less than its cardiac stimulating action and the resulting effect is an elevation of arterial pressure. The purpose of the meeting was to bring together scientists of fourteen countries ranging from the chemist to the surgeon, who usually do not speak a common language and for whom it would be quite difficult to follow the latest developments in fields allied to, but still some what removed from their basic interest. The supernatant contained most of the activity.
A further goal for the chemist is to differentiate the various activities, i. Care must be taken in interpreting the micropuncture data, or the contribution of pial arterioles to cerebrovascular resistance may be erroneously understimated. Eledoisin showed a very marked tachy-phylaxis, but no cross-tachyphylaxis towards the two other peptides, indicating a different site of action from that of bradykinin and kallidin. Severely low blood pressure can deprive the brain and other vital organs of oxygen and nutrients, leading to a life-threatening condition called shock. The void volumes of the columns were determined with blue dextran. No evidence was obtained during these experiments to indicate that bradykinin actively dilates the pulmonary veins. There was considerable improvement in symptoms and in the blood-pressure and pulse-rate changes during treatment with propranolol, fludrocortisone, or cypro-heptadine.
The ratios between equieffective doses of substance P and bradykinin on the forearm blood flow were about 1:10 at i. Dilatation of the coronary arteries was found to be β1- and not β2-mediated. Case reports of 2 patients are presented who have medullary bone disease and pancreatic disease. Blood flow to hand increased during such infusions of bradykinin, but blood flow to forearm was not altered significantly. Stellate ganglion block increased the resting blood flow as well as the vasodilating action of both polypeptides. Vasoactive peptides such as kallidin and bradykinin and other agents such as acetylcholine and isopropylarterenol exerted transient increases in renal blood flow and decreases in renal resistance. Distensibility of the superficial forearm and hand veins was measured in 25 patients with varicosity of the saphenous veins, and in 25 control subjects.
In summary, we have shown that in endotoxemia activation of B1 receptors causes coronary vasodilation via endothelial prostacyclin release. It has been well established that, with few exceptions 31, 46 , the peptides exert directly a vasodilator action in many species of animals 1, 4—6, 11, 12, 25, 39, 41, 44, 46, 47. The bone lesions may be acute or chronic and are the result of medullary necrosis. A plethysmographic technique was used to measure forearm blood flow and to estimate forearm venous tone. The 25th International Congress on Physiological Sciences held in Munich the following week also provided the impetus for the organization of this satellite symposium on vasopeptides.
Subsequently, reports on the physiological, pharmacological, pathological, and clinical importance of kinins, kallikrein, and eledoisin were presented. The results were compared under test conditions utilizing both direct renal arterial and systemic intravenous infusions. The large number of biological effects that can be demonstrated in extremely low doses raised many questions about the importance of the kinins in the physiological and pathological processes Stürmer, 1966; Wiegershaiisen and Paegelow, 1966; Erdös, 1966; Werle, 1967; Habermann, 1968. The increase in pulmonary vein pressure with no change in left atrial pressure suggested a throttle valve action of the pulmonary veins, probably at the veno-left atrial junction. This was followed in loose order by reports dealing with the structure of some newer peptides, with kininogen, and with enzymes that release or inactivate peptides. The ability of kallikrein gene delivery to produce a wide spectrum of beneficial effects makes it an excellent candidate in treating hypertension, cardiovascular and renal diseases.
Graham in some phases of the work is greatly appreciated. The presence of D-Arg9 in bradyklnln also prevented the hydrolysis, notwithstanding that this D-amino acid Is only in adjacent position to the bond split by the peptidase. A method for the determination of inulin in biological fluids using a modified anthrone reagent is described. Heart rate increased during the hypotensive period, but subsequently returned toward preinfusion levels. The peptides used were donated by the following individuals : Dr. Propranolol was more potent in respect of coronary artery than of other β1-mediated responses, and available data suggest that this potentially adverse characteristic may be peculiar to this drug. Total calf flow and venous volume were measured by venous occlusion plethysmography while venous flow axial velocity was determined by the transit time of 131-I albumin from calf to inguinal region.
Local intravenous epinephrine administration induced venoconstriction and increased venous flow velocity. The same format is used in the second section on water efflux. It is often associated with shock, though not necessarily indicative of it. The normal group showed no significant changes in any of these values after alcohol intake. Recent evidence suggests an important role for the kallikrein-kinin system in the pathophysiology of hyperalgesia, arthritis, inflammatory bowel disease, pancreatitis, asthma and endotoxemia. From numerous observations obtained from clinical and experimental models of diabetes, hypertension, cardiac failure, ischemia, myocardial infarction and left ventricular hypertrophy, it can be assumed that the reduced activity of the local kallikrein-kinin system may be instrumental for the induction of cardiovascular related diseases. The physiologoical role of locally liberated bradykinin from tissue kallikrein is still not known.